LESSONS  IN 

PATHOLOGICAL 
HISTOLOGY 


BY 

GUSTAVE  ROUSSY  AND    IVAN  BERTRAM) 

PROFESSEUR  AGREGE.'cHEF  DBS  TRA-  CHEF  DE  LABORATOIRE    DELKGUE    A    LA 
VAUX        PRATIQUES       D'ANATOMIE  CLINIQUE  DBS   MALA 

PATHOLOGIQUE  A  LA  FACULTE  VEUSES  DE  LA  FACt  I   I  I 

DE   PARIS  Dl     I'ARIS 


TRANSLATED  FROM  THE  SECOND  FRENCH  EDITION    BY 

JOSEPH  McFARLAND,  M.D.,  Sc.D. 

PROFESSOR    OF  PATHOLOGY  AND  BACTERIOLOGY  IN  THE  MEDICAL  DEPARTMENT  OF 
THE  UNIVERSITY   OF    PENNSYLVANIA 

ILLUSTRATED   WITH    124   ENGRAVINGS 


LEA   &   FEBIGER 

PHILADELPHIA   AND   NEW   YORK 
1922 


A  P  < 


BiOLOG'i 
LIBRAR 


COPYRIGHT 

LEA  &  FEBIGER 

1922 


PRINTED  IN  U.  S.  A. 


PREFACE. 


THIS  interesting,  and  intensely  practical  little  book  is  novel 
in  almost  every  particular  and  has  no  parallel  among  the  books 
offered  to  students  of  medicine. 

It  bears  the  same  relation  to  pathologic  histology  that  a 
" dissector"  does  to  anatomy;  it  is  a  self-instructor,  teaching 
the  salient  features  of  the  tissues  studied.  It  is  not  a  text- 
book of  pathology,  nor  can  the  student  possibly  suppose  that 
it  can  take  the  place  of  one;  it  is  not  a  hand-book  of  technic. 
It  is  a  guide,  and  a  very  intelligible  one,  to  the  microscopic 
study  of  morbid  tissues.  It  may  not  contain  all  of  the  sections 
that  the  student  is  called  upon  to  study — they  differ  in  different 
institutions — but  it  contains  enough  to  teach  him  the  correct 
method,  and  gives  the  most  important  facts,  after  which  new 
material  may  be  approached  without  hesitation  and  with  full 
confidence  that  the  same  methods  applied  will  yield  the  same 
satisfactory  results. 

The  approach  to  the  diagnosis  is  always  systematically  made : 
The  student  is  first  told  what  should  be  seen  with  the  naked 
eye,  then  what  is  to  be  seen  with  the  low-power  lens,  and  finally, 
if  necessary,  what  with  the  high-power  lens. 

Particular  fields  for  examination  with  the  higher  powers  are 
frequently  indicated  upon  the  drawing  by  lines  inclosing  small 
squares. 

When  the  book  is  opened,  the  right-hand  pages  are  found 
to  show  the  beautiful  drawings  of  M.  Bessin,  to  which  in  this 
American  edition  have  been  added  additional  ones  by  Mr. 
Erwin  Faber,  so  drawn  as  to  correspond  with  the  originals,  from 
which  it  is  impossible  for  one  not  in  possession  of  the  French 
copy  to  differentiate  them.  On  the  left-hand  page  is  a  text  cor- 
related with  the  illustration,  and  telling  how  one  should  proceed 
in  studying  it.  Although  brief,  this  text  is  descriptive,  critical 
and  diagnostic,  and  transforms  the  book  from  an  atlas  to  a 
guide  by  being  of  a  value  equal  to  the  illustrations. 

40770?  J"  McF" 


LESSONS  IN  PATHOLOGICAL 
HISTOLOGY. 


INTRODUCTION 

AT  the  beginning  of  this  little  book,  intended  to  direct  the 
student  in  his  first  steps  in  the  study  of  pathological  histology, 
are  brought  together  a  few  elementary  facts  about  practical 
microscopy.  It  is  done  as  briefly  as  possible,  in  the  hope  that 
it  will  be  appreciated  by  these  for  whom  it  is  intended. 

Certain  details  of  histological  technic  are  important  in  the 
successful  interpretation  of  microscopic  preparations. 

Only  the  most  important  of  them  will  be  mentioned,  espe- 
cially as  nearly  all  of  the  sections  have  been  fixed  and  stained 
in  the  same  manner. 

It  is  indispensable  to  follow  certain  rules  in  the  interpretation 
of  histological  slides,  and  it  is  through  lack  of  knowing  and 
observing  them  that  beginners,  too  soon  employing  high-power 
lenses,  lose  themselves  in  the  reading  of  the  sections  and  commit 
the  grossest  errors  of  interpretation. 

A  histological  diagnosis  ought  to  be  conducted  much  as  a 
clinical  diagnosis  at  the  bedside.  It  is  only  after  having  exposed 
the  patient  and  examined  him  in  his  entirety,  that  the  clinician 
goes  on  to  the  successive  methods  of  inspection,  palpation, 
auscultation,  etc. 

Methods  of  Using  the  Microscope  and  Interpreting  the  Sec- 
tion.—A  microscope  consists  of  a  stand,  an  optical  system 
(objectives  and  oculars),  and  an  illuminating  apparatus  com- 
prising an  Abbe  parabolic  condenser,  a  mirror  and  an  iris 
diaphragm. 

The  Abbe  condenser  should  not  be  employed  with  very  low- 
power  lenses  whose  magnification  does  not  exceed  that  of  a 
hand  lens.  Besides  the  diminution  of  the  light  that  results 


18       LESSONS  IN  PATHOLOGICAL  HISTOLOGY 

from  its  employment  in  such  cases,  images  of  the  window, 
the  wall  and  other  objects  are  apt  to  appear  in  the  field  of 
vision.  The  condenser  is,  therefore,  to  be  removed  from  the 
optical  axis  with  such  powers.  It  is,  however,  necessary  with 
middle-  and  high-power  lenses,  but  it  ought  to  be  placed  at 
some  distance  from  the  object  in  order  that  the  best  illumina- 
tion be  obtained  and  distinctness  of  vision  secured.  The 
higher  the  magnification,  the  nearer  the  condenser  must  be 
brought  to  the  stage;  with  an  oil-immersion  lens  it  should  be 
in  immediate  contact  with  the  slide. 

The  mirror  has  plane  and  concave  sides,  each  of  which  sub- 
serves a  special  purpose.  The  concave  side  should  be  used 
when  the  source  of  light  is  small,  as  in  artificial  light;  the  plane 
side  for  natural  light. 

The  iris  diaphragm  serves  to  cut  out  the  excessively  oblique 
rays  of  light  when  high-power  lenses  are  used.  How  widely  it 
should  be  open  or  how  tightly  closed  is  a  matter  that  can  only 
be  learned  by  experience.  As  a  matter  of  fact,  the  student 
should  open  and  close  it  more  or  less  with  each  change  of  mag- 
nification and  with  each  different  object  examined,  as  with 
different  degrees  of  light  different  structural  details  are  brought 
out. 

The  Objectives  and  Oculars.— The  microscopes  used  by 
students  vary  in  different  laboratories,  some  being  provided 
with  two,  some  with  three  objectives,  according  to  the  different 
character  of  the  work  to  be  done.  When  this  is  histological 
only,  two  objectives — a  low  power  and  a  high  power — are  all 
that  are  required;  if  bacteriological  or  cytological  work  is  to 
be  included  it  may  be  necessary  to  add  another— higher  power— 
or  even  an  oil-imersion  lens.  It  will  be  supposed  that  the 
student  using  this  manual  finds  his  equipment  to  consist  of 
two  objectives— a  low  power  and  a  high  power.  He  usually 
also  receives  two  oculars  by  which  to  reach  the  extremes  of 
high  and  low  powers  within  the  range  of  his  objectives.  In 
general,  however,  it  is  best  to  work  only  with  the  low-power 
ocular  as  it  affords  the  best  definition. 

The  Low-power  Objective. — It  is  with  this  magnification  that 
the  study  of  every  microscopic  section  ought  to  be  begun.  It 
gives  a  general,  that  is,  a  topographical  view  of  the  whole 
section,  and  enables  the  different  component  tissues  and  their 


INTRODUCTION  19 

relations  to  be  determined,  and  the  parts  requiring  further 
examination  to  be  recognized.  For  example,  in  a  section  of 
a  uniform  structure,  such  as  the  pulmonary  tissue,  the  low 
power  enables  sections  of  the  bronchi  and  bloodvessels  quickly 
to  be  found,  and  if  there  be  any  deeply-colored  masses,  such 
as  bronchopneumonic  areas  or  tubercles  present,  they  quickly 
catch  the  eye.  Again,  in  sections  of  any  part  of  the  wall  of 
the  alimentary  tract  it  easily  discovers  any  breach  of  surface 
continuity  such  as  constitutes  an  ulceration. 

The  examination  with  the  low-power  lens  ought,  therefore, 
be  continued  for  some  time  as  it  enables  the  trained  eye  not 
only  to  discover  the  organ  concerned,  but  also  to  make  a  pre- 
sumptive diagnosis  of  its  principal  lesions. 

The  Medium-power  Objective. — Should  there  be  a  medium- 
power  lens,  its  use  will  in  most  cases  suffice  to  complete  the 
diagnosis. 

The  High-power  Objective. — This  should  only  be  employed  to 
complete  the  observation.  It  shows  but  a  very  circumscribed 
field  of  the  section,  and  its  chief  uses  are  for  defining  the  cyto- 
logical  and  nuclear  structural  details— protoplasmic  granules, 
vibratory  cilia,  mitotic  figures,  etc. 

THE  ELEMENTARY  PRINCIPLES  OF  HISTOLOGICAL 
TECHNIC. 

Only  the  methods  of  fixing  and  staining  indispensable  to  the 
interpretation  of  the  sections  described  in  this  manual  will  be 
mentioned. 

i.  Fixation.— Pieces  of  tissue  selected  for  histological  exami- 
nation should  be  immersed  in  a  preserving  fluid  for  the  purpose 
of  fixing  their  structure  by  coagulating  the  albumins  with  the 
least  possible  modification  of  their  cells.  According  to  the 
size  and  fixation  of  the  blocks  of  tissue  will  their  cellular  char- 
acteristics be  well  preserved. 

(a)  Pieces  of  tissue  obtained  from  surgical  operations  and 
fixed  upon  the  spot  may  be  regarded  as  in  a  state  of  perfect 
preservation. 

(b)  Pieces  of  tissue  taken  from  autopsies  made  twenty-four 
hours  after  death  will  be  found  in  a  very  unequal  state  of 
preservation.     They   have    not   only   been   subjected    to    the 


20       LESSONS  IN  PATHOLOGICAL  HISTOLOGY 

disadvantages  of  putrefaction,  but  also  to  the  action  of  auto- 
lytic  enzymes,  whose  effects  are  especially  marked  upon  the 
alimentary  mucosa.  The  adrenal  body  and  the  cerebellum  also 
rapidly  show  the  effects  of  postmortem  change. 

In  all  such  cases  care  must  be  taken  not  to  confuse  the  results 
of  the  postmortem  changes  with  the  pathological  lesions.  In 
general,  the  cadaveric  or  postmortem  changes  are  uniformly  dis- 
tributed throughout  the  entire  section,  all  of  the  elements  of  the 
same  kind  being  similarly  affected  and  about  to  the  same  degree. 

Among  the  fixatives  most  commonly  used  the  following  may 
be  mentioned. 

(a)  Formaldehyde.— It  is  employed  in  a  dilution  of  i  part  of 
the  commercial  40  per  cent  solution  with  9  parts  of  water.1    It 
also  forms  the  base  of  such  other  fixatives  as  Bouin's  solution 
which  is  made  up  of  75  parts  of  a  saturated  solution  of  picric 
acid,  20  parts  of  formaldehyde  and  5  parts  of  acetic  acid.    This 
solution,  however,  frequently  imparts  an  undesirable  yellowish 
color  to  the  tissue. 

(b)  Corrosive  Sublimate. — This  may  be  employed  in  the  form 
of  a  solution  composed  of  corrosive  sublimate  3  parts,  acetic 
acid  i  part  and  distilled  water  100  parts.     It  also  enters  into 
the  composition  of  numerous  other  fixatives  such  as  Domi- 
mici's  solution  which  is  made  of  a  saturated  aqueous  solution 
of  corrosive  sublimate  100  cc,  formaldehyde  15  cc  and  enough 
tincture  of  iodine  to  give  the  fluid  a  port-wine  color. 

Whenever  solutions  of  corrosive  sublimate  are  used  as  fixa- 
tives it  is  necessary  to  wash  the  tissue,  after  twelve  to  twenty- 
four  hours'  immersion,  in  running  water  for  twenty-four  hours. 
The  chemical  has  the  disadvantage  of  forming  a  combination 
with  the  albumins  of  the  tissue  which  subsequently  appears 
in  the  form  of  a  black  acicular  crystalline  deposit.  This  some- 
times causes  confusion  with  blood  and  other  pigments  naturally 
present,  though  its  acicular  form  ought  to  enable  it  to  be  easily 
recognized.  It  is,  however,  best  to  remove  it  by  adding  tincture 
of  iodine  to  the  alcohols  subsequently  used  for  dehydration. 

2.  Imbedding  and  Cutting. —After  fixation  the  blocks  of  tissue 
are  subjected  to  washing,  progressive  dehydration  by  passage 
through  alcohols  of  increasing  strength,  and  are  finally  imbedded 

1  Better  results  result  from  the  use  of  physiological  salt  solution  instead 
of  water  as  the  diluent. 


INTRODUCTION  21 

in  some  substance  such  as  paraffine  or  celloidin  that  subsequently 
solidifies  sufficiently  to  permit  them  to  be  cut  into  sections 
from  5  to  10  microns  in  thickness,  with  a  microtome. 

If  the  edge  of  the  microtome  knife  is  uneven  the  sections 
may  present  a  striated  appearance  which  deforms  their  struct- 
ural elements.  The  parallel  direction  of  these  striae  enables 
them  to  be  recognized  as  artefacts. 

The  colloid  substance  of  the  thyroid  body  commonly  presents 
a  "picket  fence,"  or  palisade  appearance,  but  that  is  an  arte- 
fact that  depends  rather  upon  the  peculiar  fragility  of  the 
substance  itself  than  upon  defects  in  the  edge  of  the  knife. 

3.  Staining. —The  sections,  fastened  to  the  slides,  are  stained 
in  various  ways,  of  which  only  these  most  commonly  used  will 
be  mentioned,  as  it  is  most  important  to  simplify  the  technic 
as  much  as  possible  for  beginners,  and  employ  as  nearly  as 
as  possible  the  same  methods  for  all  of  the  different  tissues 
described. 

Hematoxylon.—This  is  a  basic  dye  extracted  from  logwood. 
It  stains  the  nuclei  of  the  cells  a  deep  blue  color. 

Eosin.—  This  is  an  acid  anilin  dye.  It  stains  connective- 
tissue  fibers  a  pale  rose  color  and  striated  and  unstriated  mus- 
cular fibers  a  bright  red. 

Van  deserts  Stain.—  This  consists  of  a  solution  made  up 
as  follows: 

I  per  cent  aqueous  solution  of  acid  fuchsin    ....  5  cc 

Saturated  aqueous  solution  of  picric  acid        .      .      .      .       100  cc 

It  is  used  as  a  counter-stain  with  iron  hematoxylon.  With  the 
combination  vascular  connective  tissue  is  stained  intense  red 
by  the  acid  fuchsin,  the  protoplasm  of  the  cells  is  colored  yellow 
by  the  picric  acid  and  the  nuclei  are  black  from  the  iron  hema- 
toxylon. 

The  method  is  especially  appropriate  for  the  demonstration 
of  the  vascular  connective  tissue  in  the  study  of  the  various 
scleroses— chronic  nephritis,  cirrhosis,  pancreatitis,  etc. 

Acid  Orcein. — This  stain  is  composed  of: 

Orcein i  gr. 

Hydrochloric  acid       . i  cc 

96  per  cent  alcohol i  oo  cc 

The  orcein  has  an  elective  affinity  for  the  elastic  tissue  which  it 
colors  brown-black. 


THE  NORMAL  LUNG. 

1.  Low-power    Lens. — The    pulmonary    tissue    presents    an 
alveolar  appearance  that  is  recognizable  even  to  the  naked 
eye,  and  depends  upon  the  presence  of  numerous  spaces,  the 
pulmonary  alveoli,  of  very  similar  size  and  shape  in  the  normal 
lung. 

These  air  spaces,  irregularly  lozenge  shaped,  are  bounded  by 
sinuous  walls,  the  inter  alveolar  septa. 

Here  and  there,  as  in  the  center  of  the  drawing,  bloodvessels 
and  air  tubes  are  seen  cut  transversely  or  longitudinally,  and 
for  the  most  part  grouped  together  in  the  connective-tissue 
trabeculce  or  broncho-vascular  axes  of  the  pulmonary  structure. 

Black  patches,  anthracotic  accumulations,  especially  distinct 
in  the  neighborhood  of  the  bronchial  tubes,  are  almost  con- 
stantly present  in  the  lungs  of  the  adult  and  the  aged,  and  in 
the  reading  of  the  microscopic  sections  form  a  precious  element 
in  making  the  differential  diagnosis  of  the  organ.  The  lungs 
with  their  associated  lymph  nodes  are  the  organs  most  frequently 
pigmented  with  carbon  particles. 

The  alveoli,  broncho- vascular  axes  and  anthracotic  collections 
form  a  triad  that  should  always  be  looked  for  with  care  in 
recognizing  the  pulmonary  parenchyma. 

If  the  section  reaches  to  the  external  surface  of  the  lung  it 
may  include  the  pleura  which  is  composed  of  a  layer  of  vascular 
connective  tissue  covered  by  endothelium. 

2.  High-power  Lens. — The   structural  details  now  become 
more  distinct.     The  interalveolar  septae  seem  to  be  composed 
of  cells  of  a  shape  varying  in  different  cases.     In  lungs  obtained 
at  autopsy  some  of  them  are  often  found  to  have  detached  and 
to  lie  free  in  the  air  spaces.     In  certain  areas  the  cells  seem  to 
be  gathered  together  in  masses— an  appearance  that  results 
from  the  tangential  sectioning  of  the  wall  of  one  or  several 
alveoli. 

In  the  interalveolar  septae  there  are  capillary  bloodvessels 
which  in  the  normal  state  contain  only  one  or  two  red  blood 
corpuscles. 

If  the  section  be  stained  with  orcein  (as  in  Fig.  2)  elastic 
fibers  can  be  seen  in  the  interalveolar  septae  in  the  form  of 
fine  filaments  of  dark  brown  or  black  color,  insinuating  them- 
selves between  the  cells  and  the  capillaries  and  passing  from 
one  alveolus  to  another. 

22 


Cartilage  in  the  bronchial  wall. 


Bronchiole 

Bronchial 
vessel 

Pulmon- 
ary artery 
Pulmon- 
ary alveoli 


Pulmon- 

'     A    -/*•* 

ary  vessel. 

Pulmon- 

ary vein 
containing 
"  laked 

1    blood. 
Pulmon- 

o-rtr  tT^ccf*! 

Fig.  1. — Normal  lung.     Lung  of  a  suicide. 
Staine/i  with  hematoxylon  and  eosin.     Magnified  25  diameters. 

This  shows  the  characteristic  triad  upon  the  finding  of  which 
the  diagnosis  of  the  pulmonary  tissue  depends— the  pulmonary 
alveoli,  the  vessels,  which  in  this  case  contain  some  laked  blood, 
and  the  bronchial  tube  with  its  supporting  cartilage.  The  anthra- 
cotic  accumulations  cannot  be  easily  recognized  with  this  magni- 
fication. 


In  the  neighborhood  of  the  broncho- vascular  apparatus  .the 
high-power  lens  enables  one  to  recognize : 

1.  The  bronchioles,  or  air  tubes,  with  a  cylindrical  epithelial 
lining  supported  upon  a  connective-tissue  wall,  at  the  periphery 
of  which,  in  those  of  middle  and  large  size,  there  may  be  carti- 
laginous plates.     These  appear  blue  violet  in  sections  stained 
with  hematoxylon  and  eosin. 

2.  The   bloodvessels   which   are   easily   recognized   by    their 
smooth  endothelial  lining,  which  contrasts  strongly  with  the 
columnar  epithelium  so  distinctly  seen  in  the  bronchial  tubes. 

The  branches  of  the  pulmonary  artery  can  be  distinguished 
from  those  of  the  pulmonary  veins  by  the  thickness  of  their 
walls,  and  by  the  fact  that  they  are  usually  empty  while  the 
veins  usually  contain  blood. 

NOTE.— The  anatomical  unit  of  pulmonary  structure  is  the 
lobule^  but  for  its  demonstration  special  methods  of  prepara- 
tion— insufflation,  injection  of  coagulable  substances,  serial 
sections,  etc.— must  be  resorted  to,  so  that  it  does  not  clearly 
appear  in  microscopic  sections.  It  is  of  interest  in  enabling 
the  morphological  structure  of  the  lung  to  be  understood,  but 
has  very  little  importance  in  pathological  histology. 

In  any  section  of  a  diseased  lung  the  lesions  of  the  alveoli, 
the  bronchioles,  the  interalveolar  septae  and  the  vessels  are 
the  important  features  for  study,  their  lesions,  through  synthe- 
sis of  the  findings,  enabling  a  diagnosis  of  the  condition  to  be 
reached. 

The  pulmonary  alveolus  ought  to  be  regarded  as  the  unit 
of  structure  in  pathological  histology.  It  may  be  compressed 
or  collapsed  as  in  the  fetus  (atelectasis) ,  distended  to  bursting 
(emphysema),  or  filled  with  morbid  products  (edeinatous  fluid 
blood,  fibrin,  pus,  etc.),  in  edema,  infarction,  pneumonia,  or 
bronchopneumonia  (alveolitis  serosa,  hemorrhagica,  fibrinosa, 
purulenta,  respectively).  The  same  is  true  of  the  bronchial 
tubes. 

It  is  only  after  study  of  the  various  elementary  lesions  and 
their  distribution  in  the  section  that  the  whole  can  be  inter- 
preted, purely  contingent  lesions  cast  aside  and  proper  evalua- 
tion given  the  most  important. 

The  condition  of  the  pleura  should  also  be  considered  if  the 
surface  of  the  lung  be  included  in  the  section. 


24 


Elastic 
fiber. 


Tangen- 
tial sec- 
tion of  an 
alveolus. 


Tangen- 
tial sec- 
tion of  an 
alveolus. 

Alveolar 
space. 

Alveolar 
wall. 


Respira- 
tory epi- 
thelium. 
Capillary 


Fig.  2. — Normal  lung.     Lung  of  a  suicide. 

Stained  with  acid  orcein.     Magnified  250  diameters. 

The  reticulum  of  elastic  fibers  is  shown  colored  black  by  the 
orcein.  At  two  points,  above  and  to  the  right,  and  below  and  to 
the  left,  the  alveolar  epithelium,  seen  in  full  face  instead  of  in  pro- 
file, seems  to  occur  in  plates.  This  is  the  result  of  tangential 
cutting  of  the  section. 


25 


PULMONARY    EMPHYSEMA   AND   CONGESTION. 

The  Diagnosis  of  the  Organ.— This  is  easy  to  make:  One 
recognizes  the  pulmonary  alveoli  and  sees  in  the  center  of  the 
drawing  a  section  of  a  broncho- vascular  axis  containing  a  bron- 
chial tube  with  its  lining  of  cylindrical  epithelial  cells.  A 
pulmonary  artery  and  vein  and  patches  of  carbon  particles 
are  also  shown. 

The  Diagnosis  of  the  Lesion. — That  which  at  once  strikes 
the  observer  is  the  great  size  of  certain  of  the  air  cells.  There 
are  all  intermediate  stages  between  normal  alveoli  and  enor- 
mous cavities.  Many  of  the  alveolar  walls  have  ruptured 
(emphysema),  though  they  appear  distinctly  thicker  than  in 
the  normal  lung  because  of  distention  of  the  capillaries 
(congestion) . 

The  air  cells  are  almost  entirely  empty  (contain  air),  but 
in  some  a  few  red  blood  corpuscles  may  be  seen. 

A  higher  power  lens  permits  the  alveolar  walls  to  be  studied. 
In  sections  stained  with  hematoxylon  and  eosin,  they  are 
almost  entirely  composed  of  extremely  dilated  capillaries  con- 
taining numerous  red  blood  corpuscles.  Sometimes  they  make 
hernial  protrusions  into  the  alveolar  cavity,  and  even  rupture 
here  and  there,  permitting  the  escape  of  the  corpuscles  into 
the  air  cells  (hemorrhagic  alveolitis). 

The  nuclei  visible  in  the  section  belong,  for  the  most  part 
to  the  endothelial  cells  of  the  capillaries. 

It  is  scarcely  possible  to  find  any  of  the  alveolar  epithelial 
cells,  either  because  of  pathological  alteration  (desquamation 
or  degeneration),  or  because  of  cadaveric  alteration  (defective 
fixation  of  very  fragile  elements). 

In  sections  especially  stained  with  orcein  (Fig.  5,  B),  which 
brings  out  the  elastic-tissue  network  of  the  pulmonary  structure, 
it  is  possible  to  study  its  alterations — fragmentation  and 
extension— which  are  very  important  in  emphysema. 

The  elastic  tissue  of  the  alveolar  wall  is  found  to  be  composed 
of  delicate  fibrillae,  colored  black,  mostly  cut  longitudinally 
and  following  a  course  that  spreads  out  according  to  the  obliquity 
of  the  section.  To  the  right  in  the  drawing  a  black  stippling 
results  from  transverse  section  of  the  fibers.  To  the  left  a 
capillary  in  the  alveolar  wall  distinctly  shows  its  elastica. 
The  interalveolar  walls  are  stretched  and  thinned. 

There  are  no  changes  in  the  microscopic  appearance  of  the 
bronchial  tubes. 

26 


Pulmon- 
ary artery 


Bron- 
chiole 
without 
cartilagin- 
ous sup- 
port. 

Blood  in 
an  alveo- 
lus. 


Inter- 
alveolar 
septum. 


Emphy-  [ 
sematous 
bladder. 


Fig.  3. — Pulmonary  emphysema  and  congestion. 
Staining  with  hematoxylon  and  eosin.     Magnified  20  diameters. 

//  is  the  lung  of  an  old  man  with  chronic  emphysema  and  con- 
gestion. The  unequal  size  of  the  pulmonary  alveoli,  the  rupture  of 
the  interaheolar  septce  and  the  thickness  of  the  alveolar  walls  from 
distention  of  the  capillaries  are  to  be  particularly  noted. 


27 


All  of  the  bloodvessels,  large  and  small,  are  dilated  and 
distended  with  blood  and  show  as  bright  red  dots  in  the  section. 
About  the  larger  vessels  there  is  a  slight  increase  in  the  con- 
nective tissue  (beginning  sclerosis). 

The  condition  corresponds  with  what  is  called  essential 
emphysema,  by  which  is  meant  that  neither  in  the  gross  morbid 
specimen  nor  in  the  microscopic  section  can  any  explanation 
of  the  distention  of  the  air  cells  be  found. 

In  subsequent  descriptions,  and  especially  in  that  of  bron- 
chopneumonia,  it  will  become  evident  that  though  emphysema 
sometimes  occurs  as  a  primary  lesion,  it  also  occurs  in  associa- 
tion with  other  important  conditions  such  as  fibrinous  alveolitis, 
purulent  alveolitis,  hemorrhagic  alveolitis  and  edema,  which 
take  precedence  over  it  in  importance  in  the  interpretation  of 
what  is  seen  in  the  section  and  to  which  it  is  secondary. 

Resume. — Pulmonary  emphysema  with  beginning  sclerosis 
and  intense  congestion.  The  latter  may  be  referred  in  part,  if 
not  altogether,  to  the  agonal  condition  of  the  circulation.  It 
is  common  in  lungs  removed  at  autopsy,  and  no  importance 
should  be  attributed  to  it  unless  it  is  found  in  association  with 
other  conditions  evincing  its  priority. 


28 


Normal 
alveolus. 


Small 
hemor- 
rhage. 
Dilated 
capillary. 


Septum 
with  a 
capillary. 


Elastic 
fibers. 


Inter- 

Iveolar 
septum. 

1  Longi- 
f  tudinal 
J  elastic 
J  fibers. 

]  Trans- 
(  versly  cut 
[  elastic 
J  fibers. 


Fig.  4. — Pulmonary  emphysema  and  congestion. 

A. — Stained  with  hematoxylon  and  eosin.  Magnified  200 
diameters.  With  this  power  the  congestive  changes  of  the  inter- 
alveolar  wall  can  be  better  appreciated. 

B. — Stained  with  orcein.  Magnified  250  diameters.  With 
this  stain  the  elastic  fibers  are  brought  out  with  distinctness  on 
account  of  their  black  color. 


29 


PULMONARY  INFARCTION. 

The  section  consists  of  a  hemorrhagic  focus  and  its  immediate 
surroundings.  To  the  naked  eye  it  seems  to  be  homogeneous. 

Diagnosis  of  the  Organ.— At  the  lower  edge  of  the  section 
one  can  make  out  the  alveolar  network,  and  by  moving  it 
about  (under  a  low-power  lens)  can  find  sections  of  vessels  and 
a  bronchial  tube  (the  last  is  not  shown  in  the  drawing). 

i.  Low-power  Lens.—Ey  passing  from  the  center  to  the 
periphery  of  the  hemorrhagic  focus  three  zones  may  be  dis- 
tinguished : 

(a)  A  central  zone  which  is  the  seat  of  a  hemorrhage  that 
has  effaced  all  the  details  of  pulmonary  structure,  and  appears 
to  be  composed  of  nothing  but  densely  packed  red  blood  cor- 
puscles  whose   contours   are   still   quite   distinct.     Occasional 
leukocytes  appear,  the  nuclei  of  both  lymphocytes  and  poly- 
morphonuclears  being  stained  blue  by  the  hematoxylon.     Dis- 
seminated  throughout   the   area   occasional   blackish   crystals 
of  hematoidin,  derived  from  the  hemoglobin,  may  be  seen. 

(b)  A  median  zone  in  which  the  alveolar  contours  can  be 
distinguished  though  the  air  spaces  are  all  filled  with  blood. 
The  alveolar  walls  seem   to  have   disappeared,   their  places 
being  taken  by  blood  pigment  and  cellular  debris. 

(c)  An  outer  zone  in  which  the  pulmonary  tissue  has  reacted 
—inflammatory  zone.     Here  the  alveoli  are  filled  with  a  finely 
meshed  fibrinous  exudate   (stained  red),  mononuclear  leuko- 
cytes, desquamated  endothelial  cells  and  a  great  number  of 
crystals  of  hematoidin  either  free  or  in  the  interior  of  mono- 
nuclear  cells  (macrophages). 

In  the  upper  right-hand  fourth  of  the  drawing  the  cause  of 
the  pulmonary  hemorrhage  appears  as  a  branch  of  the  pul- 
monary artery  completely  obliterated  by  a  large  clot  adhering 
to  the  inner  wall  about  its  entire  circumference,  the  result 
of  thrombosis  or  embolism.  The  upper  part  of  the  thrombus  is 
formed  of  red  corpuscles  densely  packed  together  as  in  the 
hemorrhagic  focus  in  the  neighboring  lung,  but  in  the  lower 
part  its  structure  is  less  homogeneous  and  pigment  crystals 
appear.  Lastly,  at  the  periphery  of  the  thrombus  there  are 
minute  vessels  of  new  formation  whose  office  it  is  to  transform 
it  into  viable  organized  tissue  (organization  of  a  thrombus). 

Resume.— Pulmonary  infarction  from  embolism.  It  is  not 
recent  as  is  shown  by  the  transformation  of  the  blood  pigment 
and  the  penetration  of  new  vessels  into  the  thrombus. 

30 


Throm- 
bosed 
pulmon- 
ary artery 
containing 
a  partly 
organized 
clot. 

New 
vessels. 


Fibrinous 
alveolitis. 

Small 

hemor- 

rhagic 

area. 


:    ' 


Fig.  5. — Pulmonary  infarction. 


I  Central 
zone  of 
massive 
hemor- 
rhage. 

Small 
throm- 
bosed 
vessel. 


II  Median 
zone 

apoplectic 
zone 


Hemor- 

rhagic 

alveolitis. 


Ill  Zone  of 

fibrinous 

reaction. 


Congested 
vessels. 


Stained  with  hematoxylon  and  eosin.     Magnified  25  diameters. 


Embolic  pulmonary  apoplexy  or  infarction  complicating  acute 
endocarditis.  The  thrombus  which  closes  the  pulmonary  artery 
is  penetrated  by  newly-formed  bloodvessels  and  is  undergoing 
organization.  Passing  outward  from  the  thrombosed  artery  as  a 
center,  the  infarction  shows  three  zones:  I,  a  zone  of  massive 
hemorrhage;  II,  a  zone  of  hemorrhage  in  which  some  of  the  alveolar 
walls  can  still  be  seen;  and  III,  a  zone  of  fibrinous  alveolitis.. 

31 


FIBRINOUS  PNEUMONIA. 
Croupous  Pneumonia. 

Diagnosis  of  the  Organ. — This  is  difficult  in  consequence  of 
the  uniformity  of  the  inflammatory  reaction.  The  character- 
istic triad— alveolar  network,  vessels  and  bronchi  and  anthro- 
cotic  accumulations  can  be  found  only  in  the  less  atypical  areas. 

The  lesion  is  very  uniform  and  consists  of  a  fibrinous  exudate 
filling  all  of  the  alveoli,  giving  the  pulmonary  tissue  a  gross 
quality  comparable  to  the  liver,  hence  the  term  hepatization. 
From  the  red  color  resulting  from  the  presence  of  large  numbers 
of  red  corpuscles  in  the  alveoli  it  is  called  red  hepatization. 

i.  Low-power  Lens. — The  exudate  consists  of  a  network  of 
fine  meshes  of  eosin  staining  material,  whose  organized  form 
contrasts  with  the  red  amorphous  character  of  the  serous  fluid 
found  in  edema. 

Sometimes  the  fibrinous  meshwork  is  separated  from  the 
alveolar  wall  by  a  narrow  interval,  this  appearance  being  caused 
by  the  contraction  effected  by  the  reagents  used  in  fixing  and 
preparing  the  tissue.  Some  of  the  bundles  of  filaments  pass 
through  ruptures  in  the  alveolar  walls  and  connect  with  exudate 
in  neighboring  air  cells. 

In  the  meshes  of  the  network  are  numerous  formed  ele- 
ments—large endothelial  cells  with  abundant  cytoplasm,  poly- 
morphonuclear  and  mononuclear  leukocytes  and  red  blood 
corpuscles. 

The  fibrin  and  red  blood  corpuscles  characterize  the  stage 
of  pneumonia  called  red  hepatization  (fibrinous  alveolitis).  In 
the  subsequent  stage  the  fibrin  disappears,  and  polymorpho- 
nuclear  leukocytes  fill  the  alveoli— gray  hepatization  (purulent 
alveolitis) . 

In  sections  stained  with  methylene  blue  or  by  Gram's 
method  numerous  lanceolate  diplococci— pneumococci— can  be 
seen  in  the  exudate. 

The  proportion  of  elements  in  the  alveoli  varies  very  slightly; 
the  lesion  is  uniform  and  diffuse,  and  quite  different  from  that 
found  in  bronchopneumonia  (see  Fig.  7)  in  which  it  occurs  in 
scattered  foci. 

The  respiratory  epithelium  is  desquamated;  the  capillaries 
are  much  dilated,  often  ruptured,  thus  permitting  the  red 
corpuscles  to  escape  into  the  exudate. 

The  smaller  bronchi  sometimes  contain  a  serofibrinous  exudate 
mixed  with  polymorphonuclear  leukocytes. 

Lastly,  the  pleura,  not  shown  in  the  drawing,  but  often 

32 


affected  in  pneumonia,  may  be  covered  with  a  thick  layer 
of  fibrin  (false  membrane). 

Resume. — Fibrinous  alveolitis,  corresponding  to  the  second 
stage  of  frank  acute  pneumonia.  The  uniformity  of  the  lesion 
shows  it  to  be  diffuse  and  lobar,  at  least  if  the  fragment  was 
not  taken  from  a  nodule  of  bronchopneumonia,  which  histo- 
logical  examination  alone  does  not  enable  one  to  determine. 


Alveolar 
wall. 

Inter- 
alveolar 
fibrinous 
filaments. 


Intact 
bronchus 

Poly- 
nuclears 
Desqua- 
mated 
epithelial 
cells 


- 

*    •^'^r<t-.--.^ Si •"-••'*  •  ^  ^•i 


Red  blood 
corpuscles. 


Vessel. 


Fibrin 
Inter- 
alveolar 
fibrinous 
filaments. 
Ruptured 
alveolar 
wall. 


Fig.  6. — Fibrinous  pneumonia.     (Fibrinous  alveolitis.) 
Stained  with  hematoxylon  and  eosin.     Magnified  200  diameters. 

Section  made  from  a  solid  block  of  frank  acute  pneumonia  in 
an  adult  whose  other  lung  showed,  at  autopsy,  the  lesion  of  gray 
hepatization.  The  disturbance  is  precisely  the  same  throughout 
the  entire  section  and  consists  in  fibrinous  aheolitis,  characterized 
by  the  presence  of  fibrinous  reticula,  red  blood  corpuscles,  poly- 
morphonuclear  leukocytes  and  desquamated  epithelium  in  the  alveoli. 
It  is  the  stage  of  red  hepatization,  the  second  stage  of  pneumonia. 

3  33 


BRONCHOPNEUMONIA. 

Diagnosis  of  the  Organ.— With  a  low-power  lens  one  can 
recognize  the  alveolar  network  and  sections  of  bronchi  and 
vessels  in  the  less  affected  pale  parts  of  the  section. 

Diagnosing  the  Lesion.— That  which  at  once  attracts  atten- 
tion is  the  occurrence  of  the  lesion  in  foci,  indicated  by  scattered 
dark  areas;  nodules  of  peribronchial  disturbance  separated 
by  healthy  tissue. 

Low-power  Lens.— In  the  upper  part  of  the  drawing  the 
debris  of  bronchial  epithelium  is  recognizable  by  the  columnar 
epithelium,  arranged  in  palisade  form,  mixed  with  numerous 
abnormal  polymorphonuclear  leukocytes.  Near  the  bronchial 
tube  there  is  an  arteriole.  Both  of  these  are  in  a  broncho- 
vascular  axis  about  which,  according  to  the  classical  concep- 
tion, the  peribronchial  nodule  has  developed.  Passing  from  the 
center  to  the  periphery,  which  is  not  always  easy  to  recognize 
when  the  diseased  areas  are  numerous  and  close  together;  the 
alveoli  present  extremely  diverse  appearances.  But  that  which 
characterizes  bronchopneumonia  is  the  extreme  variety  of  the 
alveolar  lesions.  These  consist  of: 

1.  Fibrinous  alveolitis,  much  like  that  of  fibrinous  pneumonia, 
with  network  of  fibrin  enmeshing  epithelial  cells,  leukocytes 
and  red  blood  corpuscles. 

2.  Purulent  alveolitis,  where  the  fibrinous  network  has  dis- 
appeared, giving  place  to  an  enormous  number  of  partly  degen- 
erated polymorphonuclear  leukocytes,  with  deeply  staining  nuclei 
from  which  the  nuclear  network  has  disappeared  (pycnosis). 

Sometimes  the  alveoli  are  filled  with  polymorphonuclear 
leukocytes  mixed  with  desquamated  epithelial  cells  and  red 
blood  corpuscles;  sometimes  they  are  bathed  in  serous  fluid 
(edematous  alveolitis} ;  sometimes  the  alveolar  walls  have 
ruptured  and  large  purulent  cavities  formed. 

The  large,  middle-sized  and  small  bronchial  tubes  are  filled 
with  pus— a  condition  constant  in  bronchopneumonia,  but 
not  a  reliable  character  upon  which  to  base  a  differential 
histological  diagnosis  between  fibrinous  and  lobular  or  bron- 
chopneumonia. It  is  the  lobular  distribution  and  the  dissem- 
ination of  the  lesions  that  characterize  bronchopneumonia. 

In  the  zones  of  the  pulmonary  parenchyma  that  appear 
healthy  (not  shown  in  the  drawing)  contingent  alveolar  lesions 
may  be  observed— alveolar  edema,  emphysema,  etc. 

Resume.— The  extreme  variety  of  the  alveolar  lesions,  their 

34 


occurrence  in  disseminated  foci  and  their  frequent  arrangement 
about  the  broncho-vascular  axes  are  characters  that  permit  the 
diagnosis  of  acute  broncho  pneumonia. 


Branch  of 
the  pul- 
monary 
artery. 


Poly- 

morpho- 

nuclear 

cells. 

bathed  in 
edema- 
tous fluid. 

Fibrinous 
alveolitis. 


Desqua- 
mated 
bronchial 
epithe- 
lium. 

Alveolus 
filled  with 
poly- 
morpho- 
nu  clear 
cells. 

Purulent 
alveolitis. 


Endothe- 
lial  cell. 


Edema- 
tous  fluid 
with  poly- 
morpho- 
nuclear 
cells   (ede- 
matous 
alveolitis. 


Fig.  7.— Acute  bronchopneumonia. 
Stained  with  hematoxylon  and  eosin.     Magnified  150  diameters. 

Bilateral  nodular  bronchopneumonia.  The  specimen  was 
secured  from  the  lung  of  a  child  that  died  of  measles.  With  this 
magnification  the  peribronchial  distribution  of  the  areas  does  not 
appear.  The  diversity  of  the  alveolar  changes,  which  vary  from 
edematous  to  purulent  infiltration  is  to  be  noted.  There  are  also 
marked  changes  in  the  bronchial  epithelium. 


35 


MILIARY  TUBERCULOSIS  OF  THE  LUNG. 

With  the  naked  eye  the  rose-colored  centers  of  small  dark 
patches  the  size  of  millet  seeds  can  easily  be  distinguished. 

Diagnosis  of  the  Organ.— With  a  low  magnification  the 
diagnosis  of  the  organ  can  easily  be  made  through  the  presence 
of  the  pulmonary  alveoli,  vessels  and  bronchial  tubes, 

Diagnosis  of  the  Lesion.— The  dark  patches  are  formed  of 
dense  rose-violet  masses,  the  topography  of  which  is  quite 
irregular  and  without  the  peribronchial  arrangement  seen  in 
bronchopneumonia.  Examination  of  the  nodules  shows  them 
to  be  miliary  tubercles  in  different  stages  of  development. 

In  some  the  center  is  occupied  by  one  or  more  giant  cells 
and  is  surrounded  by  a  zone  of  epithelioid  cells,  large  and  trans- 
parent, with  elongated  and  frequently  bilobed  nuclei;  while  the 
periphery  is  composed  of  lymphoid  cells  whose  nuclei,  colored  a 
deep  blue,  are  surrounded  by  a  very  small  amount  of  protoplasm. 

In  others  the  center  is  caseous,  with  occasional  fissures 
brought  about  through  the  action  of  the  fixing  reagents.  The 
giant  cells  are  then  crowded  to  the  periphery  or  absent. 

Sometimes  the  tubercles  tend  to  fuse  into  conglomerate  masses 
of  much  greater  size. 

In  the  upper  left-hand  portion  of  the  drawing  (Fig.  8)  there 
is  a  structure  that  can  easily  be  confounded  with  a  tubercle. 
It  is  rounded  and  has  a  central  lumen  limited  by  a  very  indis- 
tinct undulating  line.  It  is  a  small  artery  with  a  thickened 
diseased  wall.  Such  arteritis  is  frequent  in  tuberculosis. 

Between  the  tubercles  the  pulmonary  parenchyma  shows  a 
variety  of  lesions: 

(a)  Catarrhal  aheolitis  with  desquamated  epithelial  cells  and 
some  red  blood   corpuscles   escaped   through  rupture  of   the 
alveolar  capillaries,  which  are  everywhere  dilated  and  filled 
with  blood. 

(b)  Purulent   alveolitis,    characterized   by   accumulations   of 
polymorphonuclear  leukocytes  in  alveoli  with  normal  or  ruptured 
walls. 

(c)  Edematous  aheolitis,   characterized  by  the  presence  of 
serous  fluid  in  the  air  cells. 

There  are  no  lesions  of  the  bronchial  tubes,  the  epithelium  of 
whose  walls  is  intact. 

Resume. — Pulmonary  tuberculosis  in  which  the  tubercles  are 
fairly  discrete  and  in  various  stages  of  development,  some 
already  having  undergone  caseation  in  the  center:  Miliary 
Tuberculosis. 

36 


Artery 

with  peri- 

arteritis. 


Catarrhal 
alveolitis. 


Miliary 
tubercle 
with  giant 
cells. 

Edema- 

tous 

alveolitis. 


Giant  cell. 


Fig.  8. — Miliary  tuberculosis  of  the  lung. 

Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

//  is  a  case  of  bilateral  miliary  tuberculosis  of  the  lungs  in  an 
adult.  The  tubercles  -visible  to  the  naked  eye  are  a  little  larger 
than  the  fine  gray  granules  of  the  granulia.1  Further  they  are 
distributed  in  loose  clusters  about  the  bronchi,  and  not  at  hazard 
as  are  the  granulia.  The  dissemination  of  the  tuberculous  areas 
is  to  be  noted.  All  are  about  the  same  size,  but  not  all  contain 
giant  cells.  Between  the  tubercles  the  alveoli  show  contingent 
lesions  such  as  edematous  and  catarrhal  alveolitis. 

1  Granulia  is  a  name  given  by  Empis  for  an  inflammatory  condition  that 
like  tuberculosis  is  characterized  by  the  presence  of  small  granulations 
upon  the  serous  surfaces  and  in  the  organs.  It  is  not  recognized  in  America, 
and  the  term  is  almost  never  heard. 


THE  MILIARY  TUBERCLE. 

The  tubercle  selected  as  the  type  was  taken  from  a  section 
of  pulmonary  tuberculosis. 

Diagnosis  of  the  Organ. — This  is  easily  made  through  the 
presence  of  an  alveolus  which  shows  in  the  upper  left-hand 
part  of  the  drawing,  and  a  part  of  a  bronchial  wall  seen  in 
the  upper  right-hand  corner. 

Diagnosis  of  the  Lesion.— With  the  low-power  lens  the 
tubercle  can  be  divided  schematically  into  three  zones. 

1.  A  central  part  of  a  more  or  less  bright  rose  color. 

2.  A  median  part  composed  of  a  crown  of  pale  cells  and   of 
giant  cells. 

3.  A  peripheral  part,  dense  and  formed  of  blue  cells. 

This  is  the  miliary  tubercle  in  the  stage  of  its  full  develop- 
ment, i.  e.,  with  central  caseation.  In  the  same  section  some 
can  be  found  in  less  advanced  stages  with  or  without  central 
giant  cells,  and  almost  entirely  composed  of  lymphocytes. 

With  the  high-power  lens  the  same  tubercle  shows: 

1.  The  central  zone  formed  of  caseous  material  and  structure- 
less or  finely  granular,  taking  the  cosine  strongly,  with  occa- 
sional cracks  caused  by  retraction  during  fixation. 

2.  The  middle  zone  composed  of  epithelioid  and  giant  cells. 
The  giant  cells  are  of  very  irregular  shape,  and  frequently  of 
indefinite  outline  because  their  prolongations  insinuate  them- 
selves between  the  neighboring  cellular  elements.     The  proto- 
plasm is  granular,  homogeneous  and  acidophil;    the  nuclei  are 
numerous,  sometimes  20  or  30,  in  general  arranged  near  the 
periphery  of  the  cell  in  the  form  of  a  coronet  when  complete,  or 
a  horse-shoe  when  incomplete. 

The  giant  cells  of  tumors  (giant-cell  sarcoma)  do  not  have  the 
peripheral  arrangement  of  the  nuclei  and  their  cytoplasm  is 
basophilic,.  i.  e.,  colored  by  the  hematoxylon.  The  foreign- 
body  giant  cells  may  have*  the  nuclei  pushed  out  toward  the 
periphery,  but  the  cytoplasm  is  always  basophilic  in  reaction. 

The  epithelioid  cells  surround  the  central  caseous  mass  as 
a  bluish  ring.  They  are  polyhedral  cells  with  abundant  dis- 
tinct protoplasm,  and  an  elongated,  often  bilobed,  nucleus. 
The  lymphocytes  insinuate  themselves  in  greater  or  smaller 
numbers  between  them.  Through  pressure  the  epithelioid  cells 
become  fused  into  masses  that  eventuate  in  giant  cells. 

In  sections  stained  by  Ziehl's  method,  tubercle  bacilli  may 
be  seen  in  the  centers  of  the  giant  cells  and  between  the  epithe- 
lioid cells. 

3.  The  peripheral  zone  of  lymphocytes  contrasts  with  the 

38 


preceding  both  by  its  density  and  by  its  color.  The  nuclei 
are  small,  dark  and  are  surrounded  by  very  scanty  cytoplasm. 
If  the  central  area  of  caseation  be  large  the  softened  and 
liquified  material  may  be  evacuated  through  a  neighboring 
bronchial  tube  in  the  form  of  a  sudden  profuse  expectoration 
(vomica)  and  a  cavity  thus  be  formed. 


Catarrhal 

and  hem- 

orrhagic 

alveolitis. 


Lympho- 
cytes. 

III.  Lym- 
phoid 


Two  giant 
cells. 


Interior  of 
a  bron- 
chial tube. 
Dilated 
capillary. 
Bronchial 
epithe- 
lium. 


II.  Zone 
of  epithe- 
lioid  and 
giant  cells. 


I.  Zone 
of  casea- 
tion. 


Fig.  9. — Miliary  tubercle 
Stained  with  hematoxylon  and  eosin.     Magnified  300  diameters. 

The  figure  shows  under  a  high  magnification  a  part  of  a  tubercle 
taken  from  a  case  of  ulcerative  tuberculosis  of  the  pulmonary  apex. 
It  shows  the  different  zones  of  the  miliary  tubercle  very  distinctly. 
I.  Zone  of  central  caseation.  II.  Zone  of  epithelioid  and  giant 
cells.  III.  Zone  of  lymphoid  cells.  About  the  tubercle,  desquama- 
tion  of  the  alveolar  epithelium  (catarrhal  alveolitis},  and  dilated 
capillaries  with  blood  in  the  alveoli  (hemorrhagic  alveolitis),  both 
of  which  are  contingent  lesions. 

39 


TUBERCULOUS  BRONCHOPNEUMONIA. . 

Naked-eye  Examination.  — This  shows  a  series  of  dark  patches 
scattered  over  a  clear  field. 

Diagnosis  of  the  Organ.— This  is  made  by  the  recognition 
of  the  alveolar  network,  the  bronchial  tubes  (almost  normal), 
and  of  the  bloodvessels. 

Diagnosis  of  the  Lesions. — Low-power  Lens. — The  patches 
riddling  the  pulmonary  parenchyma  resemble  those  of  the 
ordinary  bronchopneumonia,  but  differ  from  them  in  that 
their  staining  reaction  varies  from  the  center  to  the  periphery. 
They  are  most  frequently  grouped  about  the  bronchial  tubes. 

High-power  Lens. — Here  are  found  for  study: 

1.  The  inflammatory  areas. 

2.  The  bronchi  and  alveoli  in  the  intermediate  zones,  with 
their  principal  and  contingent  lesions. 

1.  The    Inflammatory   Areas:    These    consist    of   rounded 
formations   having   the   structure   of   miliary   tubercles,   with 
caseous  centers,  giant  cells,  epithelioid  cells  and  lymphocytes. 

Besides  these,  above  and  to  the  left,  above  the  bronchial 
tube,  in  the  drawing,  there  are  conglomerate  tubercles,  closely 
pressed  together.  Such  an  assembly  of  small  rounded  grayish 
tubercles  in  the  lung  is  visible  to  the  naked  eye.  It  is  composed 
of  young  tubercles  without  central  caseation. 

In  the  middle  of  the  drawing  there  are  two  dark  patches 
consisting  of  structureless  caseous  granular  masses,  colored 
bright  red  by  the  eosin.  About  them  are  giant  cells,  epitheli- 
oid cells  and  lymphocytes.  When  the  process  of  caseation 
becomes  more  advanced  the  caseous  material  is  eliminated  by 
the  bronchi  and  gives  rise  to  the  tuberculous  cavities. 

2.  The  Pulmonary  Parenchyma:     At  the  periphery  of  less 
confluent  tuberculous  masses  the  pulmonary  alveoli  are  found 
distended,  with  the  walls  ruptured  (emphysema),  either  empty, 
or  filled  with  serous  fluid  (edema). 

Elsewhere,  but  not  shown  in  the  drawing,  there  may  be 
alveolar  catarrh,  with  desquamation  of  the  epithelial  cells, 
hemorrhagic  alveolitis,  fibrinous  alveolitis  with  delicate  net- 
work of  fibrin  fibrillae  containing  desquamated  epithelial  cells 
and  leukocytes— purulent  alveolitis  in  which  the  alveoli  are 
filled  with  degenerated  polymorphonuclear  leukocytes. 

The  bronchioles  are  normal. 

Resume. — The  distribution  of  the  lesion  in  foci  about  the 
bronchi  permits  the  diagnosis  of  bronchopneumonia;  the 
presence  of  the  caseation  and  giant  cells,  that  of  tuberculosis: 
Tuberculous  bronchopneumonia. 

40 


Nearly 
normal 
bronchial 
tube. 


3  conglom- 
erated 
miliary 
tubercles 
with  giant 
cells. 


Bronchus. 


Emphy- 

sematous 

bladder. 


Central 

zone  of 

caseation. 


Granular    j   jj 
tissue. 


Distended 

(emphyse- 

matous) 

alveolus. 


Fig.  10. — Tuberculous  catarrhal  pneumonia. 
Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

It  is  a  case  of  chronic  tuberculous  broncho  pneumonia  in  an  old 
man.  Note  the  peribronchial  arrangement  of  the  broncho  pneu- 
monic nodule,  the  zones  of  caseation  (of  which  there  are  two),  and 
the  numerous  young  miliary  tubercles  with  giant  cells.  The 
bronchi  are  normal. 


41 


MASSIVE  CASEOUS  PNEUMONIA. 

Diagnosis  of  the  Organ.— This  is  difficult  to  make  as  the 
whole  section  is  formed  of  a  compact  and  uniform  mass.  An 
experienced  eye,  however,  is  able  to  recognize  the  alveolar 
reticulum  at  several  points.  It  is  ill-defined  and  badly  colored 
but  recognizable. 

The  most  striking  feature  of  the  lesion  is  the  presence  of  a 
finely  granular  substance  colored  red  by  eosin,  a  character  by 
which  the  caseous  tuberculous  substance  can  be  recognized. 
But  here  one  has  to  do  with  a  diffused  caseation  not  localized 
in  the  central  part  of  a  tubercle. 

This  caseous  mass  occupies  the  median  zone  of  the  section. 
Below,  a  fine  bluish  reticulum  shows  against  a  reddish  back- 
ground. It  is  formed  of  elastic  fibers,  the  skeletons  of  the 
alveolar  walls  that  have  resisted  the  process  of  caseation, 
strongly  stained  by  the  hematoxylon.  They  are  grouped  in 
parallel  fasciculi,  free,  without  branchings,  distinctly  limited 
to  the  periphery  of  alveoli  in  which  all  the  other  elements — 
epithelial  cells,  capillaries,  etc.— are  subject  to  the  necrotic 
change. 

The  alveolar  spaces  contain  filaments  of  fibrin  and  some 
scarcely  recognizable  elements,  such  as  desquamated  epithelial 
cells  and  leukocytes. 

In  the  upper  part  of  the  drawing  the  reaction  zone  of  the 
pulmonary  parenchyma  can  be  seen,  following  the  usual  com- 
monplace type  of  catarrhal,  fibrinous  and  purulent  alveolitis 
with  dilatation  of  the  interalveolar  capillaries. 

Between  this  zone  of  commonplace  pneumonia  and  the 
massive  caseation  there  is  a  transition  zone  which  explains 
the  histogenesis  of  the  principal  lesion.  The  fibrinous  exudate 
disappears;  polymorphonuclear  leukocytes  and  desquamated 
epithelial  cells  fill  the  alveoli.  All  of  these  elements,  as  well 
as  the  interalveolar  walls  lose  their  staining  properties,  and 
little  by  little  take  on  the  uniform  rose  tint  of  the  complete 
caseation. 

Resume. — The  nature  of  the  lesion  with  necrosis  terminating 
in  complete  caseation  shows  that  we  have  to  do  with  a  massive 
caseous  pneumonia.  The  extent  of  the  caseous  foci  proved 
to  be  such  by  histological  study  confirmed  by  anatomo-clinical 
knowledge,  permits  us  to  speak  of  a  caseous  pneumonia.  The 
absence  of  giant  cells  should  throw  no  doubt  upon  its  nature, 
as  the  caseation  is  evidence  of  its  tuberculous  origin;  but  in 
proof  it  is  easy  to  demonstrate  the  presence  of  tubercle  bacilli 
by  staining  other  sections  by  Ziehl's  method. 

42 


Fibrinous 
alveolitis. 
I.  Zone  of 


III.  Zone 
of  caseous 
alveolitis, 
with 

preserva- 
tion of  the 
partitions 
and  elas- 
tic fibers. 


Fig.  11. — Massive  caseous  pneumonia. 
Stained  with  hematoxylon  and  eosin.     Magnified  30  diameters. 

A  section  taken  from  the  periphery  of  a  mass  of  caseous  pneu- 
monia in  a  case  of  tabes  dying  with  large  pulmonary  cavities. 

43 


TUBERCULOUS  SEROFIBRINOUS  PLEURISY. 

Diagnosis  of  the  Organ. — This  is  difficult  as  the  pulmonary 
parenchyma  is  greatly  modified.  It  is  arrived  at,  however,  by 
finding  the  pulmonary  reticulum  (in  a  part  of  the  section  not 
shown  in  the  drawing),  some  debris  of  bronchial  epithelium 
and  numerous  anthracotic  granules. 

Diagnosis  of  the  Lesion. — The  red  edge  at  the  upper  border 
of  the  drawing  corresponds  to  the  visceral  layer  of  the  pleura, 
much  thickened,  transformed  and  covered  with  false  membrane. 
Below  this  the  pulmonary  tissue  is  greatly  modified. 

Let  us  study  the  section  from  above  downward. 

1.  A  frayed-out  surface,  granular  and  somewhat  homogen- 
eous, represents  the  false  membrane  consisting  of  fibrin,   a 
frequent  form  of  reaction  on  the  part  of  the  pleural  endothelium 
against  noxious  agents. 

2.  Below  this,  a  very  thick  zone  of  granular  tissue:     little 
blue  cells— lymphocytes— distributed  throughout  a  loose  reticu- 
lum;   epithelioid  cells  mixed  up  with  lymphocytes  and  lastly  a 
caseous   mass   with   numerous    tuberculous   giant   cells   with 
nuclei   in   horse-shoe   arrangement.     These   giant   cells   must 
not  be  confused  with  the  numerous  dilated  capillaries  dis- 
tributed throughout  the  section,  and  are  usually  readily  recog- 
nized by  the  presence  of  red  blood  corpuscles  in  their  interiors. 

In  many  areas  lymphocytes,  epithelioid  cells  and  giant  cells 
are  arranged  in  such  manner  as  to  form  typical  miliary  tubercles. 

3.  Beneath  the  zone  of  the  inflamed  pleura  the  pulmonary 
tissue  is  greatly  changed.     There  are  numerous  newly  formed 
capillary  vessels,  with  or  without  carbon  particles  around  them. 
Between  them  the  pulmonary  tissue  is  formed  of  indifferent 
connective-tissue  cells  lost  in  the  meshes  of  a  fine  reticulum  of 
collogen  and  elastic- tissue  fibers.    All  of  the  elements  of  the 
pulmonary  tissue  have  disappeared  or  been  transformed. 

Resume. — Tuberculous  serofibrinous  pleurisy  with  pulmo- 
nary sclerosis  and  atelectasis.  This  is  a  classic  form  of  pleurisy 
and  is  frequently  spoken  of  as  "afebrile  "(a  f rigor e)  pleurisy, 
and  is  in  reality  always  of  tuberculous  origin.  To  make  the 
diagnosis  certain  sections  may  be  stained  by  Ziehl's  method  for 
demonstrating  the  tubercle  bacillus. 


44 


Miliary 
tubercle. 


Caseatcd 
tissue. 


2  miliary 
tubercles 
with  giant 
cells. 


Anthra- 

cotic 

granules. 


Dilated 
>  Capil- 
laries. 


Fig.  12. — Tuberculous  pleurisy. 
Stained  with  hematoxylon  and  eosin.     Magnified  25  diameters. 

//  is  from  a  case  of  tuberculous  pleurisy  with  large  serofibrinous 
e/usion,  dying  of  asystole. 


45 


EPITHELIOMA  OF  THE  TONGUE. 

Carcinoma  Spinocellulare  with  Epithelial  Pearls. 

Diagnosis  of  the  Organ.— The  section  includes  two  portions: 
That  in  the  upper  part  of  the  drawing,  uniform  in  appearance, 
represents  the  normal  organ;  the  other,  below,  the  lesion. 

In  the  normal  portion  it  is  possible  to  recognize  a  stratified 
squamous  epithelium  with  its  papillary  layer,  whose  basal 
cells  are  separated  from  the  underlying  muscular  tissue  by  a 
thin  corium.  The  muscle  tissue  is  easily  recognized  by  the 
dense  cytoplasm,  the  cross  striations  and  the  excentric  position 
of  the  nuclei.  The  muscle  fibers  are  cut  transversely,  longitu- 
dinally and  obliquely.  This  last  point,  together  with  the 
nature  of  the  covering  epithelium  and  the  absence  of  fat  cells 
enables  one  to  recognize  the  buccal  mucosa  and  to  make  a 
tentative  diagnosis  of  the  tongue. 

Diagnosis  of  the  Lesion.— In  that  portion  considered' as  nor- 
mal, there  is  keratinization  of  the  superficial  layers  of  the 
epithelium:  Fine  lamina  of  the  cornified  substance  exfoliate  as 
from  the  surface  of  the  skin.  This  marks  the  position  of  a 
plaque  of  lingual  leukoplakia,  such  as  is  common  among  smokers, 
and  in  syphilis.  At  the  edge  of  this  plaque,  which  some  regard 
as  the  precancerous  stage,  the  cancer  has  developed. 

If  the  epithelium  be  followed  from  above  downward  it  is  seen 
to  thicken  and  change  its  staining  affinities,  becoming  a  deeper 
red,  and  descending  deeply  into  the  tissue. 

These  processes  and  extensions  of  the  epithelium  thrust  their 
multiple  ramifications  along  the  interstitial  spaces  and  into 
the  muscles— a  characteristic  of  malignant  tumors. 

In  the  centers  of  many  of  the  epithelial  masses  there  are 
epithelial  pearls— cornified  cells  formed  layer  upon  layer  like 
the  skins  of  an  onion.  This  may  be  regarded  as  a  perversion 
of  the  normal  transformation  of  the  epiderm,  whose  outer  cells 
normally  cornify  and  are  shed.  In  the  cancer  masses  desquama- 
tion  is  impossible  and  the  cornified  cells  are  retained. 

Between  and  about  the  epithelial  masses  there  is  connective 
tissue  forming  a  stroma  in  which  mononuclear  and  polymorpho- 
nuclear  leukocytes  occur  in  considerable  numbers — inflamma- 
tory infiltration — whose  presence  is  to  be  referred  to  the  ulcera- 
tion  of  the  cancer  and  its  subsequent  infection. 

Resume.  — (i)  The  presence  of  the  epithelial  processes  pene- 
trating in  every  direction  into  the  depths  and  breaking  through 
the  limits  of  the  basal  membrane  (the  separation  between 
epiderm  and  corium),  (2)  the  presence  of  the  epithelial  pearls, 
and  (3)  the  presence  of  atypical  cells  with  monstrous  nuclei 
are  sufficient  to  permit  the  diagnosis  of  squamous-cell  carcinoma 
of  the  tongue. 

46 


Corium. 


Rete  Malpighii. 


Leucopl 


Longitu- 
i    dinallycut 

4 .    ..;•.-;  -"..v-r-rrrf   "  ' 

•'.•"•^•Vc  ':'  '! 

fibers. 


Trans- 
versely 
cut  mus- 
cle fibers. 


Vessel. 


Inflamma- 
tory infil- 
tration. 


Pearly 
body. 


Epithelioma 
processes. 


Fig.  13.— Epithelioma  of  the  tongue. 
Stained  with  hematoxylon  and  eosin.     Magnified  75  diameters. 

A  fragment  of  a  non-ulcerated  cancer  on  the  point  of  the  tongue, 
removed  at  operation.  The  upper  part  of  the  drawing  shows  the 
normal  tongue;  the  lower  part,  the  tumor  invading  the  submucous 
and  muscular  layers. 

47 


TUBERCULOSIS  OF  THE  TONGUE. 

Diagnosis  of  the  Organ.— When  the  section  is  examined  with 
the  naked  eye  or  with  a  low-power  lens  it  is  found  to  be  formed 
of  a  homogeneous  tissue,  one  edge  of  which  is  covered  by  a 
deeply  stained  border.  A  stronger  magnification  shows  the 
border  to  be  composed  of  a  stratified  squamous  epithelium, 
separated  by  a  thin  connective- tissue  layer  from  a  thick  mass 
of  interlacing  striated  muscle  fibers.  The  epithelium  shows  a 
cornified  surface  layer  throughout  the  greater  part  of  its  extent. 
As  in  the  preceding  illustration,  we  have  to  do  with  a  lesion  in  an 
epithelial  covered  tissue  without  adipose  tissue  and  with  a 
structure  composed  of  striated  muscle  fibers  passing  in  every 
direction.  These  are  sufficient  evidence  that  we  have  to 
do  with  the  mucous  membrane  of  the  cheek  or  tongue— at  any 
rate,  of  the  mouth. 

Diagnosis  of  the  Lesion. — Let  us  consider  the  different 
layers  passing  from  the  surface  downward.  The  superficial 
horny  layer  of  the  epithelium  is  seen  to  take  the  stain 
badly,  though  with  a  uniform  color,  and  without  showing  indi- 
vidual cellular  elements.  It  is  composed  of  thin  layers,  some 
of  which  are  in  process  of  desquamation,  and  keratinization  of 
the  epithelium— leukoplakia  lingualis.  The  epithelium  sends 
descending  processes  between  the  papillae,  which  penetrate 
more  deeply  than  normal — acanthosis — in  consequence  of  an 
inflammatory  reaction. 

Infiltrating  the  corium,  and  even  penetrating  into  the 
muscular  layer,  are  a  great  number  of  small  round  cells — 
lymphocytes. 

In  the  depths  of  the  corium,  and  even  occurring  as  deeply 
as  the  muscular  layer,  are  a  number  of  rounded  formations — 
miliary  tubercles— recognizable  through  the  presence  of  numer- 
ous giant  cells,  epithelioid  cells  and  lymphocytes.  These  do 
not  show  any  central  caseation. 

This  histological  lesion  corresponds  clinically  to  the  indu- 
rated leukoplacic  patches  of  the  tongue  so  often  superimposed 
upon  an  indurated  base,  and  makes  one  hesitate  to  make  a 
differential  diagnosis  between  tuberculosis  and  cancer. 

This  reminds  us  that  the  clinical  diagnosis  can  be  very 
difficult  and  is  often  subject  to  serious  error.  Also  that  it  is 
often  necessary  to  remove  a  fragment  of  tissue  from  the  living 
subject  in  order  to  make  a  diagnosis  and  institute  the  appro- 
priate treatment. 

Resume.  —Lingual  tuberculosis  without  ulceration,  as  the 
covering  epithelium,  is  complete  everywhere,  and  shows  only 
leukoplakia. 

48 


Corium. 


Giant 
cells. 


Giant 
cells. 

Peripheral    fc^ 

zone  of 

lymphoid 

cells. 


Miliary   _  | 
tubercle. 


Leuco- 
plakia. 


Rete  Mal- 
pighii. 


Miliary 
tubercle. 


Striated 

muscle 

fibers. 


Miliary 
tubercles 
without 
giant  cells 


Fig.  14. — Tuberculosis  of  the  tongue. 

Stained  with  hematoxylon  and  eosin.     Magnified  20  diameters. 

A  fragment  taken  from  the  edge  of  a  large  patch  of  induration 
which  simulated  cancer.  The  microscopic  examination  showed 
the  tuberculous  nature  of  the  lesion.  Above  is  the  surface  of  the 
tongue  with  some  leukoplakia,  below  are  seen  the  miliary  tubercles, 
with  numerous 'giant  cells. 


49 


SIMPLE  ULCER  OF  THE  PYLORUS. 

The  section  is  sufficiently  broad  to  include  a  part  of  the  wall 
of  the  stomach  on  each  side  of  the  ulcer.  In  the  center  of  the 
drawing  there  is  an  excavation  with  vertical  border.  This 
corresponds  to  the  seat  of  ulceration. 

Diagnosis  of  the  Organ. — One  notes  the  following: 

1.  The  epithelial  cells  of  the  gastric  mucosa.     These  are  cylin- 
drical, with  elongated  nuclei,  and  are  arranged  in  a  single 
layer  upon  a  connective-tissue  strorna,  into  which  bifurcating 
glandular  tubules  penetrate  deeply. 

2.  Below  the  gastric  glands  there  are  occasional  lymphoid 
follicles — less  numerous  than  in  the  intestine. 

3.  The  submucosa,  formed  of  dense  connective-tissue  fibers,  sep- 
arating the  mucosa  from  the  muscularis,  which  is  here  thick  and 
forms  a  true  sphincter  and  is  not  separated  into  distinct  layers. 

4.  The  serosa,  which  does  not  concern  us  except  as  a  part  of 
the  thickness  of  the  section. 

The  epithelium  and  muscularis  make  one  think  of  the  struct- 
ure of  the  digestive  apparatus;  the  absence  of  villi  cause  us  to 
exclude  the  duodenum  and  small  intestines;  the  complexity  of 
the  glandular  structure  is  not  compatible  with  the  structure 
of  the  large  intestine,  so  we  are  probably  concerned  with  a 
portion  of  the  stomach.  The  absence  of  parietal  cells  in  the 
tubular  glands  show  us  that  the  tissue  does  not  come  from  the 
fundus,  and  the  mucosa  being  formed  exclusively  of  clear 
undifferentiated  cells,  we  see  that  we  have  to  do  with  the 
pylorus.  The  thickness  of  the  muscular  layer  finally  gives  us 
the  diagnosis  of  the  precise  topography,  the  pyloric  sphincter. 

Diagnosis  of  the  Lesion. — The  borders  of  the  ulceration  are 
covered  with  epithelial  cells  that  tend  to  disappear  in  propor- 
tion as  one  approaches  the  bottom  of  the  ulcer.  The  glands 
also  become  less  distinct  and  are  stuffed  with  an  enormous 
number  of  round  cells— leukocytes.  At  the  bottom  of  the 
ulcer  the  mucosa  is  completely  absent.  The  smooth  fibers  of 
the  muscular  coat,  covered  by  a  thin  serous  exudate  containing 
a  few  pus  cells,  are  scarcely  recognizable;  they  are  trans- 
formed into  a  granulation  tissue.  On  each  side  the  muscular 
tissue  resumes  its  normal  appearance. 

The  serous  coat  consists  of  dense  and  compressed  connective- 
tissue  fibers  formed  through  a  defensive  inflammatory  reac- 
tion, resulting  in  sclerosis  by  which  the  gastric  wall  is  locally 
thickened  and  its  perforation  prevented. 

Resume.—  Simple  ulcer  of  the  pylorus:  a  common,  non-specific 
.subacute  inflammatory  lesion. 

50 


Mucous 
exudate. 
Pyloric 
glands 
cut  longi- 
tudinally. 
Pyloric 
glands 
cut  trans- 
versely. 
Lymph 
follicle. 

Sub- 
mucosa 

Ulcera-  Jl 
tion 


Vessel  in 

the  scler- 

osed 

tissue. 


Sub- 
serosa. 


Fig.  15. — Simple  ulcer  of  the  pylorus. 
Stained  with  hematoxylon  and  eosin.     Magnified  20  diameters. 

A  small  ulcer  of  the  pyloric  region  of  the  lesser  curvature  found 
at  autopsy.  The  base  of  the  ulcer  is  shown  in  the  center  of  the 
figure.  To  the  right  and  left  the  borders  seem  to  be  cut  out  of  the 
mucosa  as  with  a  punch.  Numerous  glands  of  Brunner  can  be  seen 
in  the  mucosa.  Beneath  the  ulceration  there  is  reactive  inflam- 
mation of  a  defensive  character. 


51 


CANCER  OF  THE  PYLORUS. 

Beginning  Epithelioma. 

Diagnosis  of  the  Organ.— The  section  divides  itself  into  two 
distinct  layers,  one  blue,  the  mucosa;  the  other  bright  red  and 
thicker,  the  muscularis. 

To  the  right  in  the  drawing— the  normal  part— there  is  a 
simple  layer  of  epithelial  cells,  contiguous  to,  and  descending 
into  the  mucosa  to  form  tubular  glands.  In  the  mucous  layer, 
which  is  of  the  gastro-intestinal  type,  the  absence  of  villi  shows 
that  the  section  does  not  come  from  the  duodenum  or  small 
intestine;  the  absence  of  the  cells  differentiated  into  chief  cells 
and  parietal  cells,  the  fundus  of  the  stomach.  The  presence 
of  glands  of  the  serous  type  and  the  thickness  of  the  muscular 
coat — sphincter — show  that  the  section  comes  from  the  pylorus. 

Diagnosis  of  the  Lesion.  —If  we  begin  the  study  of  the  section 
under  a  low-power  lens  and  follow  the  mucosa  from  right  to 
left  we  find  that  at  a  certain  point  the  arrangement  of  the 
cells  into  glands  disappears,  the  tubular  glands  themselves 
become  unrecognizable  and  are  replaced  by  irregular  masses 
of  cells  with  transparent  nuclei  that  sometimes  bud  and  extend 
into  the  muscular  coat.  This  is  not  a  simple  inflammatory 
infiltration  of  cells  in  which  one  scarcely  sees  anything  but 
nuclei,  but  is  composed  of  cells  that  more  or  less  closely  resemble 
the  glandular  cells  themselves.  In  certain  foci  they  may  be 
seen  originating  at  the  expense  of  the  gland  cells.  It  is  not, 
therefore,  an  inflammation  but  a  neoplasm. 

At  one  point  the  neoplasmic  cells  pass  through  the  muscularis 
and  infiltrate  the  subjacent  tissue,  hence  the  cancer— a  malig- 
nant tumor  that  progressively  invades  and  destroys  the 
neighboring  tissues — is  formed. 

In  the  submucosa  there  are  lymph  vessels  with  very  thin 
walls  filled  with  cells  identical  with  the  primitive  neoplasmic 
cells— lymphatic  neoplasmic  emboli — cells  of  the  cancer  trans- 
ported by  the  vessels  to  colonize  at  a  distance. 

Resume. — A  tumor  developed  from  the  pyloric  glands  in 
which  one  can  find  all  the  stages  of  transformation,  that  is  to 
say,  beginning  glandular  epithelioma,  of  which  the  malignant 
nature  of  the  growth  is  already  shown  by  the  invasion  of  the 
wall  of  the  stomach,  and  by  the  probable  formation  of  metas- 
tases  as  indicated  by  the  cancer  cell  emboli  in  the  lymph  vessels. 


52 


Mucosa. 


Cancer 
node. 

Lymph 
vessel 
filled  with 
neoplas- 
mic  cells. 


Muscu- 
laris. 


Fig.  16. — Beginning  cancer  of  the  pylorus. 

Stained  with  hematoxylon  and  eosin.     Magnified  45  diameters. 

The  fragment  of  tissue  was  surgically  removed  during  pylo- 
rectomy.  From  above  downward  the  drawing  shows  the  mucosa 
with  its  glands,  the  submucosa  and  the  muscularis.  Above  and 
to  the  left  of  the  mucosa  is  seen  the  beginning  of  the  glandular 
epithelioma.  The  submucosa  shows  cancer  emboli  in  the  lym- 
phatics. 


53 


TYPHOID  ULCERATION  OF  THE  INTESTINE. 

Diagnosis  of  the  Organ.— At  one  extremity  of  the  section, 
that  shown  at  the  bottom  of  the  drawing,  one  can  distinguish 
a  mucous  membrane  of  the  intestinal  type  whose  epithelial  cells 
and  nuclei  are  scarcely  visible  on  account  of  postmortem  change. 
The  glands  of  Lieberkiihn,  together  with  the  villi,  enable 
the  small  intestine  to  be  recognized.  The  epithelium  rests 
upon  a  delicate  corium  which  separates  it  from  the  muscularis 
mucosa.  Beneath  it  is  a  vascular  layer,  the  submucosa.  In 
it  there  are  no  glands  of  Brunner,  hence  the  tissue  cannot  come 
from  the  duodenum.  Below  the  submucosa  are  two  definite 
muscular  layers  which  form  the  muscularis.  The  internal  of 
these  runs  transversely,  the  outer  longitudinally.  The  organ 
is,  therefore,  the  small  intestine. 

Diagnosis  of  the  Lesion.— Following  the  mucosa  from  above 
downward  it  is  found  to  flatten  little  by  little,  its  villosities 
disappearing.  Further  down  the  glands  and  villi  reappear. 
A  careful  study  of  the  flattened  part  of  the  section  shows  that 
the  change  does  not  depend  upon  postmortem  maceration,  but 
upon  a  true  pathological  lesion  of  inflammatory  nature— ulcera- 
tion. 

As  the  edge  of  the  ulceration  is  approached  the  villi  crumble 
away,  the  cells  show  a  dull  staining  and  their  pycnotic  nuclei 
dissolve  in  the  cytoplasm.  Most  of  the  capillaries  are  con- 
siderably dilated  and  their  eosin-stained  red  corpuscles  stand 
out  distinctly  against  the  dark  blue  of  the  mucosa.  All  of 
the  tissue  of  the  mucosa  is  infiltrated  with  an  enormous  quantity 
of  small  round  cells.  In  the  normal  intestinal  wall  such  small 
round  cells  are  collected  in  aggregations  of  varying  size  in 
the  mucosa,  where  they  form  the  solitary  follicles  and  Peyer's 
patches.  Their  abundance  and  diffused  infiltration  in  this 
case  indicate  ulceration  of  one  of  Peyer's  patches.  The  bottom 
of  the  ulceration  is  formed  of  a  granulation  tissue  in  which  are 
seen  occasional  scarcely-recognizable  vestiges  of  the  epithelial 
cells  of  the  glands  of  Lieberkiihn.  The  tissue  is  very  vascular 
and  has  many  capillaries,  some  of  which  project  above  the  sur- 
face of  the  ulceration. 

Resume. — The  microscopic  examination  permits  the  diag- 
nosis of  inflammatory  ulceration  of  the  small  intestine,  but 
does  not  enable  us  to  go  further  through  histological  study 
alone.  But  the  frequence  of  typhoid  fever  and  the  ulcerations 
that  characterize  it  justify  the  opinion  that  the  lesion  is  typhoid 
ulceration.  The  final  and  definite  diagnosis  can  be  made 
only  through  the  information  gained  from  the  clinical  notes 
of  the  case  and  the  bacteriological  examination. 

54 


Layer  of 
circular 

musrlc 
fibers. 


Layer  of  > 

longitu-  $ 

dinal  mus-  ~T^ 

cle  fibers.  O 


Perito- 

neum  and 

sub- 


Muscu- 

laris 

mucosa. 

Villi. 


m 

f 


Upper 
limit  of 
the  ulcer- 
ation. 


Base  of  the  ulcer. 


Inferior 
limit  of 
the  ulcer- 
ation. 


Peyer's  patch. 


Dilated '_        _^^ 
capillaries. 


Fig.  17. — Typhoid  ulcer  of  the  intestine. 
Stained  with  hematoxylon  and  eosin.     Magnified  15  diameters. 

The  right-hand  side  of  the  drawing  shows  the  tmtcosa,  sub- 
normal above  and  below,  and  ulcerated  in  the  middle.  To  the 
left  are  the  deeper  layers  and  the  peritoneal  covering. 

55 


TUBERCULOUS  ULCERATION  OF  THE  SMALL 
INTESTINE. 

Diagnosis  of  the  Organ.— Two  parts  are  distinguishable:  The 
one  thin,  dark-colored  and  upon  which  intestinal  villa  can 
be  seen,  the  mucosa;  the  other,  thicker  and  distinct,  the  muscu- 
laris.  The  concave  lower  surface  of  the  figure  corresponds  to 
the  peritoneal  surface  covered  by  the  serosa;  the  convex  upper 
surface  to  the  mucosa.  This  curvature,  easily  seen  with  the 
naked  eye,  is  the  result  of  the  unequal  retraction  of  the  tissue 
in  the  fixing  reagents,  and  in  seeking  to  make  the  diagnosis  of 
the  organ  no  attention  should  be  paid  to  it. 

The  normal  mucosa,  well-preserved  at  the  left  hand  of  the 
illustration,  is  covered  by  a  single  layer  of  columnar  epithelium 
with  elongated  nuclei.  Here  and  there  a  goblet  cell  shows  as 
a  clear  vesicle  between  the  regular  columnar  cells.  The  epi- 
theium  dips  down  to  form  crypts — glands  of  Lieberkiihn. 
Scattered  in  large  numbers  through  the  corium,  and  occasion- 
ally gathered  together  in  masses,  are  large  numbers  of  small 
round  cells.  These  are  the  normal  lymphoid  cells  and  their 
aggregations  are  the  solitary  glands  of  the  small  intestine. 

Beneath  the  mucosa  is  the  muscularis  mucosa  and  the  sub- 
mucosa  in  which  the  absence  of  Brunner's  glands  indicates 
that  the  tissue  does  not  come  from  the  duodenum.  The  pres- 
ence of  villi  on  the  other  hand  shows  that  we  have  to  do  with 
the  jujenum  or  ileum.  Beneath  all  these  are  the  muscularis 
and  finally  the  serosa. 

Diagnosis  of  the  Lesion.— Following  the  mucosa  from  left 
to  right  of  the  illustration  it  is  found  to  entirely  disappear 
at  the  extreme  right.  This  is  because  of  ulceration,  of  which 
only  a  part  is  represented.  All  of  the  bottom  of  the  ulcer 
and  a  great  part  of  the  submucosa  consists  of  an  infiltration  of 
miliary  tubercles  with  caseous  centers  and  more  or  less  num- 
erous giant  cells. 

Resume.— The  grouping  and  distinctly  follicular  arrange- 
ment of  the  infiltration,  and  the  large  number  of  giant  cells, 
permit  one  to  affirm  the  tuberculous  nature  of  the  ulceration. 
The  final  proof— the  demonstration  of  the  tubercle  bacilli  in 
the  lesion— should  present  no  difficulties  when  the  appropriate 
staining  is  performed. 

The  lesion  is,  therefore,  tuberculous  ulceration  of  the  small 
intestine. 

56 


Villi. 

Glands  of 

Lieber- 

kuhn. 

Muscu- 

laris 

mucosa. 

Miliary 

tubercles 

with  2 

giant  cells. 


Miliary 
tubercle. 


Vessel.     H 


Circular 
muscle 
fibers. 

Longi- 
tudinal 
muscle 
fibers. 
Perito- 
neum and 
sub- 
serosa. 


Ulcera- 
tion. 


Giant 
cells. 


Infiltra- 
tion of 
lymphoid 
cells. 
Sub- 
mucosa. 
Trans- 
versely 
cut  mus- 
cle fibers 
of  the  cir- 
cular 
layer. 
Longi- 
tudinally 
cut  fibers 
of  the 
outer 
muscular 
layer. 


Fig.  18. — Tuberculous  ulcer  of  the  small  intestine. 


Stained  with  hematoxylon  and  eosin.     Magnified  20  diameters. 

//  is  a  fragment  of  a  tuberculous  ulceration  of  the  terminal 
portion  of  the  small  intestine,  the  cecum  and  "vermiform  appendix 
(with  invasion  of  the  peritoneum)  removed  at  operation.  Above, 
and  to  the  left,  is  the  surface  of  the  mucosa  with  normal  villi,  above 
and  to  the  right,  the  ulcer.  Below  the  mucosa  are  numerous  miliary 
tubercles  with  giant  cells. 


57 


NORMAL  VERMIFORM  APPENDIX. 

Naked-eye  Examination. —The  section  shows  a  circular  organ 
with  a  small  central  lumen  and  thick  walls.  If  we  examine  the 
various  layers  from  within  outward  we  find  the  following: 

1.  The  Mucosa.— This  is  formed  of  an  epithelium  composed 
of  tall  cells  placed  side  by  side,  with  occasional  goblet  cells 
between  them,  and  resembling  those  of  the  intestinal  mucosa. 
From  it,  prolongations  descend  into  the  deeper  layers  between 
collections  of  lymphoid  tissue  to  form  glands,  some  of  which 
are  cut  transversely,  some  longitudinally.     The  former  appear 
as  small  rounded  cell  collections  isolated  from  the  surface. 
The  cavity  of  the  organ  is  small  and  empty. 

2.  The  Submucosa. — Below  the  mucosa  the  corium  or  sub- 
mucosa   shows   an   enormous   infiltration   of   lymphoid    cells. 
Many  of  these  are  collected  into  definite  groups,  of  rounded 
shape,  with  pale  centers — germinal  centers — and  comprise  the 
solitary  lymphoid   follicles.     These,   similar   to   those   of   the 
other  lymphoid  organs— tonsils,  lymph  nodes,  etc.— serve  as 
precious  elements  in  the  diagnosis  of  the  appendix  vermiformis. 

3.  The  Muscularis.—This  coat  is  much  less  in  evidence  but 
it  and  the  submucosa  are  arranged  as  in  the  sections  of  the 
wall  of  the  small  intestine. 

4.  The  Serosa.—At  the  periphery  is  the  peritoneum  with  its 
subserosa,  from  one  point  upon  which  the  attachment  of  the 
meso-appendix  can  be  seen  to  arise. 

The  small  size  of  the  lumen,  the  regularly  circular  shape  of 
the  section,  the  abundance  of  the  lymphoid  deposits,  and 
finally  the  structure  of  the  walls  enable  the  diagnosis  of  the 
"vermiform  appendix  to  be  made. 

The  absence  of  mucopus  in  the  interior,  the  perfect  preserva- 
tion of  the  epithelial  layer,  the  regular  arrangement  of  the 
follicles  which  show  no  trace  of  hemorrhage  and  the  absence 
of  polymorphonuclear  leukocytes  among  the  lymphocytes  in 
the  mucous  corium  show  that  there  are  no  inflammatory  lesions, 
either  acute  or  chronic. 

Differential  Diagnosis.  — i.  An  artery  or  vein— aorta  or  vena 
cava— can  at  once  be  differentiated  by  the  absence  of  an  epithe- 
lial and  the  presence  of  the  endothelium  lining,  as  well  as  by 
the  absence  of  lymphoid  collections  from  the  walls. 

2.  A  section  of  the  esophagus  is  easily  differentiated  by  its 
interior  lining  of  stratified  squamous  epithelium. 

3.  A  section  of  a  large  bronchial  tube  is  easily  recognized 
by  the  cartilaginous  support  that  its  wall  contains,  though 
the  lining  epithelium  is  of  the  same  columnar  type  as  that  in 
the  vermiform  appendix. 

58 


Mesoappendix. 


Longi- 
tudinal 
muscle 
layer. 


Circular    \j 
muscle  layer. 


Epithe- 
lium. 


Glands  of 
1  Lieber- 
kiihn. 


Cellular 
tissue. 


Peritoneum  and 
subserosa. 


A. —  Transverse  section 
of  the  entire  appendix 
seen  under  a  low-power 
magnification — 10  diam- 
eters. 

B. —  The  inner  surface 
showing  the  mucosa  with 
the  glands  of  Lieberkiihn 
and  a  solitary  follicle 
with  its  germinative  cen- 
ter. Magnified  80  diam- 
eters. 


Fig.  19. — Normal  vermiform  appendix. 

Stained  with  hematoxylon  and  eosin.     Organ  removed  at  operation. 

59 


ACUTE  PERFORATIVE  APPENDICITIS. 

Diagnosis  of  the  Organ.— This  is  easily  made  if  attention 
has  been  paid  to  the  differential  points  given  in  the  discussion 
of  the  preceding  section. 

Diagnosis  of  the  Lesion.— That  which  at  once  attracts 
attention  is  the  communication  between  the  interior  and  the 
exterior  shown  in  the  upper  left-hand  portion  of  the  drawing. 
It  is  a  perforation. 

The  epithelium  is  slightly  altered  but  at  certain  points, 
notably  in  the  neighborhood  of  the  perforation,  it  has  dis- 
appeared. 

In  the  lumen  of  the  appendix  there  is  a  serous  exudate  con- 
taining pus  cells — polymorphonuclear  leukocytes  and  some 
mononuclear  leukocytes  with  altered  nuclei.  There  is  no 
foreign  body  in  the  interior,  nor  is  there  any  accumulation  of 
agglomerated  or  inspissated  fecal  matter,  nor  a  calculus,  nor 
any  parasite— oxyuris— such  as  are  frequently  encountered  in 
the  appendix  when  the  seat  of  pathological  change. 

If  the  epithelial  layer  does  not  show  any  pathological  altera- 
tion it  is  not  the  same  with  respect  to  the  lymphoid  deposits. 
One  cannot  help  being  struck  by  the  small  number  of  pale 
germinal  centers  that  are  present;  there  are  not  more  than  two 
or  three  such  to  be  found.  There  seems  to  be  complete  dis- 
arrangement of  the  lymphoid  cells  which  are  mixed  up  with  a 
considerable  number  of  polymorphonuclear  leukocytes.  The 
lesions  of  these  follicles  are  very  important  and  are  the  point 
of  departure  of  the  disturbance  of  neighboring  tissues — notably 
of  the  peritoneum. 

The  inflammatory  cells,  polymorphonuclears,  mononuclear 
leukocytes  and  lymphocytes  infiltrate  the  entire  thickness  of 
the  wall,  even  to  the  meso-appendix  itself. 

The  capillaries  are  very  much  dilated  and  often  ruptured, 
but  not  much  attention  is  to  be  paid  to  that,  as  it  is  commonly 
present  in  operative  cases  (false  hemorrhagic  appendicitis), 
and  is  caused  by  traumatic  injury  done  to  the  tissues  by  the 
forceps  or  the  fingers  at  the  time  of  the  operation. 

The  peritoneal  coat  is  roughened  and  is  more  or  less  covered 
with  false  membranous  deposits — fibrin — infiltrated  with  leuko- 
cytes. 

The  edges  of  the  perforation  have  a  necrotic  appearance 
and  scarcely  show  any  normal  structure  on  account  of  the 
enormous  collection  of  leukocytes  by  which  they  are  infiltrated. 

Resume.— The  presence  of  mucopus  in  the  interior  of  the 
appendix,  the  excellent  preservation  of  the  epithelial  lining 

60 


(except  at  the  point  of  perforation)  and  the  striking  changes 
in  the  lymphoid  structures  of  the  walls  indicate  the  lesion  to 
be  acute  perforative  appendicitis.  It  would  be  difficult  if  not 
impossible  to  say  from  the  examination  of  the  section  whether 
or  not  this  lesion  had  occurred  in  an  appendix  already  the 
seat  of  chronic  appendicitis. 


Perfora- 
tion. 

Muco- 
pus. 
Disap- 
pearing 
solitary 
lymph 
follicle. 
Glands  of 
Lieber- 
kiihn. 


Mesoappendix. 


Infiltration. 


Solitary 

lymph 

follicles. 


Fatty  and  areo- 
lar  tissue. 


Infiltration. 


•Fibrinous  exudate. 
Fig.  20. — Acute  appendicitis  with  perforation. 

Removed  at  operation.     Stained  with  hematoxylon  and  eosin.     Magnified 

10  diameters. 


The  perforation  is  seen  above  and  to  the  left.  The  contrast 
between  the  extensive  vascular  and  connective-tissue  lesions  and 
the  well-preserved  epithelium  is  to  be  noted.  The  solitary  glands 
have  almost  entirely  disappeared.  The  interior  contains  pus,  the 
exterior  is  covered  with  fibrinous  false  membranes.  The  meso- 
appendix,  especially  at  its  attachment  is  greatly  infiltrated  with 
inflammatory  cells. 

61 


CHRONIC  OBLITERATIVE  APPENDICITIS. 

Diagnosis  of  the  Organs.— This  is  difficult  to  make. 

Examination  with  a  low-power  lens  shows  a  section  of  a 
cylinder,  or  tube,  whose  interior  is  completely  filled  up.  Its 
walls  are  formed  of  smooth  muscular  tissue  arranged  in  two 
layers  and  about  which  there  is  a  serous  coat.  The  center  of 
the  tube  is  formed  of  connective  tissue  and  of  cells  whose 
nature  this  magnification  does  not  permit  to  be  recognized. 
The  arrangement  of  the  muscular  tissue  and  the  absence  of  any 
elastic  layer  enables  us  to  eliminate  a  bloodvessel  from  con- 
sideration and  makes  us  suspect  a  section  of  some  other  oblit- 
erated tube  such  as  as  the  vermiform  appendix  or  a  Fallopian 
tube.  Knowledge  of  the  clinical  source  of  the  material  must  be 
be  depended  upon  for  a  correct  final  diagnosis. 

Diagnosis  of  the  Lesion.— The  general  architecture  of  the 
organ  being  completely  upset,  a  greater  magnification  must  be 
employed  to  determine  the  lesion.  Having  learned  that  the 
tissue  is  vermiform  appendix,  the  first  thing  that  strikes  us  is 
the  absence  of  a  lumen,  of  a  lining  epithelium  and  of  the  glands 
belonging  to  the  epithelium,  as  well  as  the  goblet  cells  usually 
so  numerous  among  them.  Another  element  equally  character- 
istic of  the  vermiform  appendix  has  equally  disappeared,  that 
is,  the  lymphoid  tissue  with  its  follicles.  In  the  place  of  all  of 
these  elements  one  finds  only  a  dense  connective  tissue  filled 
with  cells  of  an  embryonal  appearance — lymphocytes.  It  is  a 
granulation  tissue  and  contains  numerous  young  bloodvessels— 
arterioles  with  thick  walls  and  capillaries— of  new  formation. 
Finally,  at  various  points  there  are  groups  of  fat  cells  of  adult 
type  which  give  somewhat  the  appearance  of  minute  openings 
punched  in  the  tissue.  Their  presence  is  referred  to  metaplasia 
of  the  connective  tissue  caused  by  the  inflammation.  Under 
the  influence  of  chronic  inflammation  of  the  organ  the  mucous 
corium  has  proliferated,  crowding  out  the  epithelial  and  lym- 
phoid formations.  The  sclerosis  even  extends  to  the  muscularis, 
in  which  the  fibers  can  be  seen  to  be  more  or  less  dissociated,  so 
that  the  tunic  has  a  striated  appearance  comparable  to  that 
seen  in  the  mesarterium  of  atheromatous  arteries.  The  peritoneal 
coat— serosa— is  unchanged. 

Resume.— The  absence  of  all  epithelial  and  lymphoid  ele- 
ments, the  disappearance  of  the  central  lumen  and  its  replace- 
ment by  connective  tissue  of  embryonal  character  lead  to  the 
diagnosis  of  chronic  obliterative  appendicitis. 

62 


Fatty 
sub- 
peritoneal 
tissue. 


Muscu- 
lar coat. 


Dissoci- 
ated 
muscle 
fibers. 


Longi- 
tudinal 
muscle 
fibers. 


Circular 

muscle 

fibers. 


Granula- 
tion 
tissue. 


Capillary 


Fat  cells. 


'  Arteriole. 


Fig.  21. — Chronic  obliterative  appendicitis. 

Stained  with  hematoxylon  and  eosin. 

A.— Entire  section  of  the  appendix  magnified  15  diameters. 
The  portion  included  in  the  rectangle  is  shown  in  Fig.  B. 

B. — A  portion  of  the  muscular  wall  showing  the  details  of  con- 
nective-tissue proliferation  which  end  in  the  complete  obliteration 
of  the  appendix.  Magnified  about  150  diameters. 

63 


CANCER  OF  THE  CECUM. 

Cylindrical  Cell  Carcinoma. 

Diagnosis  of  the  Organ. — At  the  upper  part  of  the  figure 
there  is  a  mucous  membrane  of  the  intestinal  type ;  in  the  lower 
part,  numerous  tubular  formations  recalling  the  structure  of 
tubular  glands. 

The  entire  thickness  of  the  mucosa  is  formed  of  tubular 
glands  side  by  side— glands  of  Lieberkiihn— resembling  those  of 
the  small  intestine.  In  the  thickness  of  the  corium  there  are 
numerous  lymphoid  deposits;  follicles  like  those  seen  in  the 
normal  small  intestine.  The  muscularis  mucosa  distinctly  sepa- 
rates the  mucosa  from  the  subjacent  formations.  The  other 
layers  of  the  intestinal  wall  are  not  distinct.  The  size  of  the 
glands  of  Lieberkiihn  and  the  absence  of  villi  enable  us  to 
recognize  the  large  intestine — colon. 

Diagnosis  of  the  Lesion.— So  long  as  a  neoplasm,  even  though 
it  be  large,  respects  the  -muscularis  mucosa  as  a  boundary  and 
develops  only  upon  one  side  of  it,  the  tumor  is  benign.  But 
if  the  boundary  of  the  muscularis  be  passed  and  the  tumor 
propagates  itself  by  contiguity  throughout  the  thickness  of 
the  intestinal  wall  the  'tumor  is  malignant — cancer.  In  this 
case  the  muscularis  mucosa  is  passed  and  the  whole  thickness 
of  the  intestinal  wall  is  invaded. 

The  tumor  is  a  typical  glandular  epithelioma,  that  is  to  say, 
a  tumor  that  deviates  but  slightly  from  the  original  glandular 
type  of  the  tissue  from  which  it  grows,  in  the  arrangement  or 
grouping  of  its  cells.  It  is  composed  of  cylindrical  tubes, 
somewhat  irregular,  and  giving  the  general  effect  of  ramifying 
and  branching  glands.  Sometimes  the  spaces  lack  distinct 
walls.  The  cells  have  atypical  structure  and  functions,  and 
show  hypertrophy  of  the  nuclei,  nucleoli,  karyokinetic  figures, 
etc. 

These  cancerous  formations  are  to  be  found  in  the  entire 
thickness  of  the  intestinal  wall  as  well  as  between  the  muscular 
fibers  as  in  the  submucosa. 

Resume.— Typical  glandular  epithelioma  of  the  colon,  infiltrat- 
ing the  wall  but  not  ulcerating  upon  the  surface.  It  is  a  form 
of  infiltrating  cancer  of  the  intestine,  different  from  the  large 
cauliflower  masses  that  ulcerate  and  bleed  upon  the  slightest 
contact— the  ulcero- vegetative  form. 


64 


Glands  of 

Lieber- 

kuhn. 

Penetra- 
tion of  the 
muscu- 
laris 
mucosa. 


Inflam- 
matory 
infiltra- 
tion. 

Pseudo- 
glandular 
cancer 
forma- 
tions. 


Muscular 
tissue. 


Fig.  22. — Cancer  of  the  cecum. 


Mucus 
exudate. 


Mucosa. 

Muscu- 

laris 

mucosa. 


Cancer. 


Stroma. 


Neoplas- 
mic  gland- 
like 
tubules. 

Cancerous 
exudate. 


Stained  with  hematoxylon  and  eosin.     Magnified  15  diameters. 

A  large  infiltrating  tumor  of  the  cecum  without  either  vegetations 
or  ulcerations.  In  the  upper  part  of  the  drawing  is  shown  the 
mucosa  separated  from  the  tumor  by  the  muscular  is  mucosa,  in  the 
center  of  which  there  is  a  breach  of  continuity  and  an  invasion  of 
the  cellular  tissue  by  the  neoplasmic  tubules.  Below  and  to  the 
right,  in  the  square  the  appearance  of  the  neoplasmic  tubules  is 
shown  in  a  magnification  of  150  diameters. 


65 


CHRONIC  PASSIVE  CONGESTION  OF  THE  LIVER. 
Liver  of  Chronic  Heart  Disease. 

Diagnosis  of  the  Organ.— Under  a  low-power  magnification 
the  tissue  appears  to  be  formed  of  strands  arranged  like  the 
spokes  of  a  wheel  about  central  points  composed  of  various 
elements.  Sometimes  these  are  constituted  by  a  single  vessel— 
hepatic  vein— sometimes,  on  the  contrary,  of  a  series  of  elements 
enclosed  in  connective  tissue — portal  space — in  which  are  found 
the  following: 

1.  A  venule,  a  ramification  of  the  portal  vein,  with  flattened 
lumen  and  thin  musculo-elastic  tunic.     In  the  interior  a  few 
red  blood  corpuscles  may  be  seen. 

2.  One  or  more  branches  of  the  hepatic  artery,  circular,  with 
thicker  walls  than  the  branches  of  the  portal  vein,  and  usually 
empty  of  blood. 

3.  Bile  capillaries,  single  or  multiple,  having  about  the  same 
diameter  as  the  hepatic  artery,  but  lined  with  a  cuboidal  epithe- 
lium (colored  blue  with  hematoxylon). 

Lastly,  in  the  periportal  tissue,  sections  of  the  -nerves  and 
lymphatics. 

The  columns  of  cells  arranged  like  the  spokes  of  a  wheel, 
the  central  or  subhepatic  veins  and  the  periportal  spaces  con- 
stitute characteristic  elements  forming  a  tripod  upon  which  the 
diagnosis  of  the  liver  depends. 

The  student,  of  course,  knows  that  the  liver  is  formed  of  a 
series  of  histological  units,  the  hepatic  lobules.  The  sub- 
hepatic  vein  represents  the  center  of  the  lobule— the  central 
zone.  The  periportal  connective  tissue  is  at  the  periphery  of 
of  the  lobule— peripheral  zone. 

Diagnosis  of  the  Lesion.— With  the  aid  of  a  low-power  mag- 
nification considerable  modifications  can  be  detected  in  the 
hepatic  parenchyma.  Even  with  the  naked  eye  or  a  hand  lens 
the  section  can  be  seen  to  be  made  up  of  a  series  of  zones  alter- 
nately dark  and  pale.  The  dark  zones  comprise  the  hepatic 
trabeculae  colored  rose- violet  by  the  eosin  and  hematoxylon  and 
corresponding  to  the  periportal  or  peripheral  zones  of  the 
lobules.  The  pale  areas,  on  the  other  hand,  scarcely  contain 
any  of  the  columns  of  liver  cells,  but  are  formed  by  a  consid- 
erable hemorrhagic  exudation  about  the  branches  of  the  sub- 
hepatic  veins— central  area  of  the  lobule.  This  arrangement, 
a  little  schematic,  corresponds  to  the  naked  eye  appearance  of 
the  liver  of  chronic  passive  congestion,  in  which  the  eye  differ- 

66 


Bile  duct. 


Portal 
space 


Fig.  23. — Chronic  passive  congestion  of  the  liver — liver  of  heart  disease. 
Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

Section  made  from  an  enlarged  liver  showing  the  nutmeg  appear- 
ance, removed  at  autopsy  from  a  patient  dead  of  asystole.  The 
parenchyma  is  differentiated  into  a  portal  zone  in  which  the 
hepatic  cell  columns  are  still  recognizable  and  perihepatic  zones 
in  which  the  parenchyma  is  destroyed  by  hemorrhage. 


entiates  dark  zones — blood — and  pale  yellowish  zones — liver 
tissue — the  alternation  of  colors  giving  the  tissue  the  so-called 
nutmeg  appearance. 

The  topographical  arrangement  seen  in  the  drawing  (Fig.  23) 
is  then  as  follows:  a  zone  of  hepatic  parenchyma,  relatively 
healthy,  is  surrounded  on  all  sides  by  hemorrhagic  areas  from 
which  all  the  parenchyma tous  tissue  has  disappeared.  The 
result  is  an  entirely  changed  appearance  of  the  liver  lobule 
which  seems  to  center  about  a  periportal  space  instead  of 
about  a  subhepatic  vein.  This  has  been  called  an  inverted 
lobule. 

If  the  examination  be  continued  with  a  higher  power  lens 
(Fig.  24)  the  following  becomes  apparent:  Leaving  the  portal 
space  (near  the  center  of  the  drawing),  the  columns  of  liver 
cells  radiate  like  the  spokes  of  a  wheel  from  a  central  point. 
Close  to  the  periportal  tissue  the  liver  cells  appear  healthy 
and  separated  from  one  another  by  scarcely  dilated  blood- 
vessels (capillaries).  But  in  proportion  as  we  pass  from  the 
portal  space  the  columns  of  hepatic  cells  appear  to  become 
shorter,  dissociated  and  separated  from  one  another  by  closely 
packed  red  blood  corpuscles. 

Still  further  toward  the  center  of  the  lobule  the  blood  capil- 
laries become  larger  and  larger  to  the  detriment  of  the  liver 
cells,  which  eventually  form  only  narrow  cellular  columns, 
flattened,  stretched  and  composed  of  only  two  or  three  cells, 
and  finally  of  single  cells — monocellular  dislocation.  In  the 
upper  right-hand  portion  of  the  drawing  there  are  considerable 
areas  of  recent  hemorrhage  in  which  the  red  corpuscles  have 
escaped  from  some  of  the  ruptured  dilated  capillaries. 

Examination  with  a  still  higher  power  lens  enables  an  esti- 
mate of  the  nature  and  severity  of  the  cellular  changes  to  be 
made.  The  protoplasm  is  found  to  be  homogeneous  or  to 
contain  fatty  or  pigmentary  granules;  the  nuclei  are  pycnotic, 
fragmented  or  have  disappeared.  These  lesions  are  especially 
marked  as  the  central  vein  is  approached. 

Resume. —Intense  congestion  of  the  hepatic  parenchyma, 
preponderating  in  the  center  of  the  lobules  where  the  blood 
stasis  tends  to  cause  dilatation  of  the  capillaries,  separation 
and  dissociation  of  the  columns  of  liver  cells,  and  ends  by 
causing  hemorrhage.  Such  are  the  lesions  of  hepatic  congestion 
in  heart  disease — hepatic  asystole. 


68 


Disso- 
ciated 
liver-cell 
columns. 


Columns 

of  liver 

cells. 


Fig.  24. — Chronic  passive  congestion  of  the  liver. 
Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

The  same  section  from  which  the  preceding  drawing  was  made, 
showing  the  edge  of  a  hemorrhagic  zone— to  the  right— and  the 
still  preserved  parenchyma  with  cell  columns  separated  by  the 
dilated  capillaries— to  the  left. 


69 


THE  FATTY  AND  CONGESTED  LIVER. 

Liver  of  Heart  Disease  and  Tuberculosis. 

Diagnosis  of  the  Organ. — With  the  low-power  lens  the  col- 
umns of  liver  cells  are  recognized,  radiating  like  the  spokes 
of  a  wheel  from  the  central— subhepatic— veins.  In  the  lighter 
colored  areas  the  periportal  connective  tissue,  with  its  usual 
inclosed  sections  of  the  portal  vein,  hepatic  artery  and  bile 
ducts,  are  easily  found— the  artery  with  its  thick  wall  by  which 
it  is  recognized,  the  bile  duct  with  its  cuboidal  epithelium. 

Diagnosis  of  the  Lesion.— One  is  at  once  struck  by  the 
appearance  of  dark  central  zones  separated  by  broad  stretches 
of  pale  tissue  in  which  the  portal  vessels  occur. 

1.  In  the  central  area— zone  about  the  central  vein— there 
are  alterations  in  the  columns  of  liver  cells  which  are  some- 
times separated  widely  by  dilated  capillaries,  sometimes  reduced 
to  small  groups  of  cells  or  to  single  cells  (mononuclear  disloca- 
tion).    In  the  hepatic  cells  themselves  there  are  small,  non- 
confluent  fatty  granules.     These  cells  frequently  have  badly 
colored  or  invisible  nuclei. 

2.  In    the    peripheral    zones — periportal    zones — there    are 
important  fatty  changes.     In  order  to  comprehend  the  his  to- 
logical  appearances  it  is  necessary  to  recall  that  every  part 
of  the  tissue  from  which  the  section  was  cut  was  immersed 
for  a  time  in  reagents— xylol,  alcohol,  chloroform,  ether,  etc.— 
which  are  fat  solvents.     It  is  on  this  account  that  the  fat 
does  not  occur  in  the  form  of  drops;    it  is  only  the  outlines 
of  the  spaces  that  formerly  contained  the  fat  that  show  (a 
negative  image).     The  little  droplets  seem  to  coalesce  to  form 
larger  and  larger  drops  until  some  of  the  cells  contain  large 
transparent  vesicles  that  displace  the  nuclei  to  the  periphery 
of  the  cell  (seal-ring  appearance),  or  may  determine  that  they 
cannot  be  seen.     The  hepatic  tissue  is  thus  gradually  replaced 
by  adipose  tissue  not  unlike  that  normally  occurring  beneath 
the  skin.    The  areas  of  fatty  change  are  arranged  about  the 
periportal  tissue  whose  vessels  and  ducts  are  otherwise  normal. 

Resume. —Liver  showing  two  types  of  lesion,  well  systema- 
tized as  regards  topography. 

i.  A  pronounced  congestion  without  hemorrhage  situated 
about  the  central  vein  and  affecting  only  the  central  area  of 
the  lobules.  2.  Fatty  disease  localized  in  the  periportal  areas. 

These  together  make  the  diagnosis  fatty  and  congested  liver. 

70 


Fatty 
degenera- 
tion. 


Portal 
vein. 

Bile  duct. 
Hepatic 
artery. 


Portal 
space. 


Hepatic 
trabeculae. 


Fig.  25. — Fatty  and  congested  liver. 
Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

A  section  of  a  large,  flabby,  reddish-yellow  liver  removed  at 
autopsy  from  a  case  of  pulmonary  tuberculosis.  In  the  center 
and  a  little  to  the  right  there  is  a  portal  space  surrounded  by  an 
extensive  zone  of  fatty  degeneration.  Above  and  below  it  are 
columns  of  hepatic  cells  separated  by  dilated  capillaries  centering 
about  a  subhepatic  vein. 


Portal 
space 


71 


FATTY  DEGENERATION  OF  THE  LIVER. 

The  liver  was  removed  from  the  body  of  a  patient  dying  of 
sarcoma,  with  profound  anemia  affecting  all  of  the  viscera. 

Diagnosis  of  the  Organ.— This  can  at  once  be  made,  as  in 
the  preceding  case,  by  observing  the  columns  of  liver  cells  and 
the  arrangement  of  the  bloodvessels  and  bile  ducts  in  the  peri- 
portal  connective  tissue. 

Diagnosis  of  the  Lesion. — A  little  to  the  left  and  slightly 
below  the  middle  of  the  drawing  there  is  an  opening  which, 
being  single,  thin-walled  and  without  surrounding  connective 
tissue,  can  be  recognized  as  a  central  vein.  From  it,  in  all 
directions,  radiate  columns  of  liver  cells  like  the  spokes  of  a 
wheel.  But  all  of  the  cells  for  a  considerable  distance  from 
the  central  vein  are  scarcely  recognizable  because  of  contained 
transparent,  highly  refracting  vacuoles— fat  droplets. 

It  will  be  observed  that  the  distribution  of  the  fatty  deposit 
in  this  case  is  exactly  the  reverse  of  that  in  the  preceding  illus- 
tration. There  it  was  at  the  periphery  of  the  lobule,  here  it 
is  at  its  center. 

The  meaning  of  visible  fat  in  the  cells  is  not  sufficiently  clear 
to  enable  positive  inferences  to  be  drawn,  but  it  is  supposed 
that  in  the  preceding  case  the  fat  brought  to  the  liver  in  the 
portal  blood  not  being  quickly  oxidized  collected  in  the  adja- 
cent cells  pending  combustion.  In  the  present  case,  however, 
it  is  supposed  that  the  malnutrition  arising  from  the  impover- 
ished condition  of  the  blood  has  been  followed  by  retrogressive 
changes  in  the  liver  cells  with  partial  chemical  dissolution  of 
the  protoplasm  and  the  setting  free  of  its  combined  fat. 

Resume. — Centrally  situated  fatty  change  of  the  liver  cells — 
fatty  metamorphosis. 


72 


Normal 

liver 

tissue. 


Fatty 
degener- 
ated liver 
Central 
vein  of 
lobule. 


Perfor- 
ated  tis- 
sue with 

vessels. 


Fig.  26.— Fatty  degeneration  of  the  liver. 
Stained  with  hematoxylin  and  eosin.     Magnified  200  diameters. 

From  a  man  dying  of  sarcoma,  with  profound  anemia  of  the 
viscera. 


73 


AMYLOID  INFILTRATION  OF  THE  LIVER. 

Section  of  a  portion  of  a  large  firm  dark-colored  liver  from  a 
case  of  chronic  pulmonary  tuberculosis. 

Diagnosis  of  the  Organ.— This  is  not  easy  on  account  of  the 
advanced  degree  of  the  morbid  process  present.  But  careful 
examination  of  the  right-hand  margin  of  the  drawing  will  show 
cells  arranged  in  columns  and  of  the  appearance  most  commonly 
seen  in  the  liver.  Near  the  center  of  the  drawing  there  is  a 
section  of  a  single,  thin-walled  vessel,  probably  a  central  vein. 
By  moving  the  section  about  it  may  be  possible  to  find  peri- 
portal  connective  tissue  with  sections  of  the  hepatic  artery, 
subportal  vein  and  bile  ducts. 

Diagnosis  of  the  Lesion.— That  which  at  once  strikes  the 
observer  is  the  fact  that  the  greater  part  of  the  sketch  represents 
a  structureless,  waxy,  amorphous,  pink-stained  substance  that 
seems  to  have  taken  the  place  of  the  liver  cells.  Upon  careful 
examination  one  can  scarcely  escape  the  impression  that  this 
is  a  new  substance  that  has  infiltrated  between  the  liver  cells 
and  crowded  them  out.  In  many  places  small  (atrophic)  liver 
cells  may  be  seen  caught  between  the  masses  of  infiltrating 
substance.  Thus  separated  from  their  fellows  and  from  their 
nutrient  supply  such  are  doomed  to  extinction. 

This  new  homogeneous  substance,  because  of  a  fancied 
resemblance  to  boiled  starch  and  because  it  sometimes  gives 
a  blue  color  with  iodine  and  sulphuric  acid,  is  called  amyloid. 
It  has  no  relation  to  the  starches,  however,  but  is  a  conjugated 
protein.  With  Lugol's  solution  it  gives  a  mahogany  red-brown 
color,  with  gentian  violet  (i  per  cent  aqueous  solution)  a  pink 
color.  It  stains  pink  with  eosin  as  in  the  case  under  observation. 

Supposing  that  the  vessel  near  the  center  of  the  drawing  is  a 
central  vein,  one  can  make  out  that  the  amyloid  deposit  occu- 
pies a  distribution  intermediate  between  a  central  and  a  periph- 
eral zone.  This  is,  however,  rarely  as  clearly  shown  as  in 
this  drawing. 

Resume. — Infiltration  of  the  intermediate  zone  of  the  liver 
lobule  by  a  translucent  waxy  substance  with  affinity  for  iodine 
and  gentian  violet — amyloid  infiltration. 


74 


Atrophic 

liver  cells 

caught  in 

amyloid 

substance. 


'    j 


Amyloid 
substance. 


1__  Central 
vein. 


Fig.  27. — Amyloid  infiltration  of  the  liver. 
Stained  with  hematoxylin  and  eosin.      Magnified  100  diameters. 


75 


LAENNEC'S   ATROPHIC   CIRRHOSIS   OF   THE 
LIVER. 

Diagnosis  of  the  Organ.— In  spite  of  the  transformation  of 
the  architecture  of  the  organ,  "the  liver  is  easily  recognized, 
thanks  to  the  triad  of  diagnostic  features  already  given :  portal 
spaces,  central  veins  and  columns  of  liver  cells. 

Diagnosis  of  the  Lesion. — One  is  at  once  struck  by  the 
presence  of  bands  of  fibrillar  tissue  that  divide  the  hepatic 
tissue  into  a  series  of  islands.  These  are  best  demonstrated 
in  sections  stained  by  Van  Giesen's  method  in  which  they 
appear  bright  red. 

The  abnormal  development  of  the  connective  tissue  is  suffi- 
cient to  lead  to  the  opinion  that  in  this  case  we  have  to  do 
with  a  sclerosis,  or,  what  comes  to  the  same  thing,  an  annular 
cirrhosis  of  the  liver. 

With  the  higher  magnification  the  more  or  less  thick  bands  of 
connective  tissue  are  found  to  be  formed  of  fine  and  feebly 
undulating  fibrillae,  in  the  meshes  of  which  there  are  small  dots 
representing  the  nuclei  of  fixed  connective-tissue  cells.  At 
certain  points,  as,  for  example,  in  the  upper  left-hand  part 
of  the  drawing,  these  round  cells  occur  in  patches  which  often 
preponderate  in  the  portal  spaces  or  beneath  the  capsule  of 
the  liver  (not  visible  here). 

Among  the  bile  ducts  some  are  large  enough  to  show  the 
cuboidal  epithelium,  but  a  great  many  are  serpentine  strands 
of  cells  without  appreciable  lumen.  It  is  a  mistake  to  regard 
these  latter  as  canaliculi  or  bile  capillaries  of  new  formation. 
More  likely  they  are  columns  of  atrophic  liver  cells  that  are 
compressed  between  the  fibers  of  the  connective  tissue — pseudo- 
canaliculi. 

The  columns  of  liver  cells  are  confused  in  their  relations  and 
in  their  structure.  They  no  longer  seem  to  radiate  from  the 
central  vein  like  the  spokes  of  a  wheel.  Furthermore,  many 
of  the  liver  cells  are  in  a  state  of  fatty  disease. 

Resume.— Annular  cirrhosis  of  the  liver  also  called  the 
bivenous  cirrhosis  because  the  bands  of  connective  tissue  con- 
nect the  central  vein  and  the  periportal  veins  and  penetrate 
into  the  lobules.  This  type  of  annular  cirrhosis  corresponds, 
from  the  microscopic  point  of  view,  either  with  the  atrophic 
cirrhosis  of  Laennec  or  with  the  hypertrophic  cirrhosis  of 
alcoholism. 


76 


Portal 
vein. 


Island  of 

hepatic 

tissue. 


Fig.  28. — Atrophic  cirrhosis  of  the  liver. 
Stained  by  Van  Giesen's  method.     Magnified  100  diameters. 

The  liver  from  which  this  section  was  made  was  removed  at 
autopsy.  It  was  atrophied,  irregular,  nodular  (hob-nail),  and 
upon  section  showed  bands  of  sclerotic  tissue  throughout  its  sub- 
stance. In  the  center  of  the  drawing  a  large  island  of  the  hepatic 
parenchyma  is  shown  surrounded  by  a  thick  ring  of  connective 
tissue  (annular  cirrhosis).  Portions  of  other  similar  islands  are 
seen  at  the  periphery. 


77 


BILIARY  PIGMENTATION  OF  THE  LIVER. 

From  a  Case  of  Chronic  Obstruction  of  the  Bile  Ducts. 

Diagnosis  of  the  Organ.— Under  the  high  power  so  limited 
an  area  of  the  liver  tissue  is  shown  as  to  make  the  diagnosis  a 
matter  of  doubt.  One  should  confirm  his  suspicion  that  the 
organ  is  the  liver  by  using  a  low-power  lens  and  finding  central 
veins  with  radiating  columns  of  liver  cells  and  periportal  con- 
nective tissue  with  hepatic  artery,  subportal  vein  and  bile 
ducts. 

Diagnosis  of  the  Lesion. — In  the  upper  right-hand  corner 
and  elsewhere  throughout  the  tissue  represented  in  the  drawing 
there  are  some  normal  liver  cells.  But  the  greater  number  of 
liver  cells  are  modified  through  the  presence  of  granules,  single 
or  in  groups,  of  varying  size  and  a  color  varying  in  intensity  to 
opaque  dark  green.  Here  and  there,  between  the  columns  of 
liver  cells,  in  spaces  supposed  to  be  bile  capillaries,  there  are 
larger  and  coarser  masses  of  the  same  substance,  sometimes 
rounded,  sometimes  clavate,  sometimes  dumb-bell  in  shape. 
These  are  composed  of  inspissated  and  more  or  less  oxidized 
bile  pigments  and  in  the  bile  capillaries  are  surrounded  by 
amorphous  translucent  matter  which  is  probably  a  protein 
constituent  of  the  bile  condensed  by  the  obstructive  process 
and  precipitated  by  the  reagents. 

The  seat  of  biliary  obstruction  is  not  shown  in  the  section. 
It  may  have  affected  the  duct  system  low  down,  even  entirely 
outside  of  the  liver  proper,  but  its  effect  has  been  the  retention 
of  the  bile  in  the  ducts  and  capillaries,  with  resulting  separation 
of  the  pigment  and  its  disposition  in  the  distribution  figured. 

Resume.— Biliary  pigmentation  of  the  liver  from  obstruction 
of  the  ducts. 


78 


Liver 
cells. 

Pigment 

in  a  bile 

capillary. 


<  .* 


jar 


^\ 


• 


@ 


.$** 


Liver 
cells. 


Kupffer 
cell  con- 
taining 
granular 
bile  pig- 
ment. 


Fig.  29.— Bile  ducts  containing  inspissated  bile,  from  a  case  of  biliary 

obstruction. 

Stained  with  hematoxylin  and  eosin.     Magnfied  500  diameters. 


79 


MALARIAL  PIGMENTATION  OF  THE  LIVER. 

From  a  Case  of  Chronic  Paludism. 

Diagnosis  of  the  Organ. — This  cannot  be  certainly  made 
from  the  limited  extent  of  tissue  shown  in  the  drawing.  In 
most  cases  the  arrangement  of  polyhedral  cells  in  columns  such 
as  shown  here  is  sufficient  to  make  the  diagnosis,  but  the 
student  should  not  be  satisfied.  What  he  first  thought  liver 
might  turn  out  to  be  part  of  the  adrenal  or  part  of  a  corpus 
luteum  of  pregnancy.  By  moving  the  section  about  under  a 
lower  magnification,  however,  the  central  veins  with  radiating 
columns  of  liver  cells  and  peripheral  connective  tissue  with 
sections  of  the  renal  arteries,  subportal  veins  and  bile  ducts 
ought  to  be  found  to  complete  the  diagnosis. 

Diagnosis  of  the  Lesion. — The  liver  cells  in  this  case  show  no 
distinct  abnormality.  But  between  them  and  in  the  capillary 
plexuses— hepatic  sinusoids— there  are  numbers  of  cells  of 
irregular  shape  and  unequal  size  whose  protoplasm  is  filled 
with  black  granules  of  fairly  uniform  size  to  such  an  extent  as 
to  make  it  difficult  to  discover  the  rather  darkly  stained  ovoid 
vesicular  nuclei.  These  are  the  cells  of  Kupffer,  and  are  phago- 
cytes. The  black  pigment  they  contain  is  hemozoin,  or  melanin, 
a  metabolic  product  of  the  malarial  plasmodium  which  is  set 
free  in  the  circulation  at  the  time  of  sporulation  and  is  subse- 
quently taken  up  by  phagocytic  cells,  among  which  are  these 
cells  of  Kupffer  in  the  liver.  The  cells  react  similarly  to  other 
minute  particles  in  the  circulation. 


80 


Normal 
liver  cells. 


Cells  of 
Kupffer? 
filled  with 
hemozoin 
granules. 


Fig.  30. — Malarial  pigmentation  of  the  liver  in  a  case  of  chronic 
paladism. 

Stained  with  hematoxylin  and  eosin.     Magnified  350  diameters. 


81 


CAVERNOUS  ANGIOMA  OF  THE  LIVER. 

In  the  substance  of  hepatic  parenchyma  without  other  defi- 
nite disturbance  the  naked  eye  discovers  a  large  bright  red 
patch  (Fig.  31,  A).  Under  the  low  power  of  the  microscope 
this  is  found  to  be  composed  of  large  spaces  whose  inner 
walls  are  lined  with  a  delicate  endothelium.  These  cavities 
are  filled  with  blood.  They  are,  in  fact,  blood  spaces,  whose 
walls  are  formed  of  a  connective  tissue  that  is  mostly  fibrous 
and  contains  very  few  cells.  A  few  capillaries  can  be  seen 
here  and  there  in  the  connective- tissue  partitions  which  form 
a  vast  network  with  coarse  meshes,  marking  out  the  spaces 
which  freely  intercommunicate  with  one  another,  forming  a 
veritable  cavernous  tissue  similar  to  that  of  the  corpus  caverno- 
sum  of  the  penis  in  the  state  of  erection. 

The  occurrence  of  such  a  tissue  in  the  liver  constitutes  an 
angioma — cavernous  angioma — a  benign  tumor,  never  giving 
metastasis. 

At  the  periphery  of  the  angioma  the  cavernous  tissue  is 
separated  from  the  hepatic  parenchyma  by  a  layer  of  connective 
tissue,  as  is  the  rule  with  benign  tumors.  There  are  no  com- 
pressed columns  of  liver  cells  at  the  edge  of  the  tumor  such  as 
one  sees  at  the  borders  of  cancer  nodules.  The  absence  of 
all  signs  of  compression  is  explained  by  the  very  slow  growth 
of  the  tumor  which  is  of  congenital  origin. 

Differential  Diagnosis.— It  is  important  not  to  confound  the 
tumor  with  a  hemorrhage :  If  it  were  such  the  trabeculae  would 
be  dissociated  and  the  hemorrhagic  foci  would  not  be  so  nicely 
delimited  by  endothelium. 

In  capillary  angioma  there  are  no  large  blood  spaces,  but,  on 
the  contrary,  very  small  spaces  corresponding  in  size  with  the 
capillaries  themselves  compacted  in  considerable  numbers. 
Capillary  angioma  is  almost  never  encountered  in  the  liver, 
but  occurs  in  the  skin  where  it  is  known  as  nevus  vasculosus. 

Resume.— Cavernous  angioma  of  the  liver,  a  small  benign 
tumor,  sometimes  single,  sometimes  multiple,  and  constituting 
a  not  uncommon  and  rarely  important  autopsy  finding. 


82 


B 

Fibrous 
septae. 


Capillary. 


Hepatic 
trabeculae. 


Angioma. 


Fibrous 
septum 
cut  trans- 
versely. 

Blood 
space. 


Communi- 
cation 
between 
two 


Endothe- 
lium. 


Dilated 
capillary. 


Fig.  31.  Cavernous  angioma  of  the  liver. 
Stained  with  hematoxylon  and  eosin. 

A. — A  section  of  the  entire  tumor,  surrounded  on  all  sides  by 
the  liver  tissue.  It  was  unexpectedly  found  at  autopsy. 

B. — Drawing  showing  the  appearance  of  the  margin  of  the 
tumor  and  the  adjacent  liver  substance.  Magnified  80  diameters. 

83 


BILIARY  ABSCESS  OF  THE  LIVER  WITH 
CIRRHOSIS. 

Diagnosis  of  the  Organ.— It  is  quite  easy  to  recognize  the 
section  as  coming  from  the  liver  because  of  the  visible  columns 
of  liver  cells  and  the  distinct  periportal  connective  tissue  with 
its  usual  accompaniment  of  vein,  artery  and  bile  ducts. 

Diagnosis  of  the  Lesion. — Two  things  attract  attention: 

1.  Dark  colored  oval  patches,  two  of  which  show  in  the  draw- 
ing and  sharply  contrast  their  dark  blue  color  with  the  generally 
rose-red  color  of  the  section.    These  are  the  abscesses. 

2.  The  excess  of  connective  tissue  in  the  form  of  islets  that 
concentrate  about  the  periportal  tissue  and  send  out  narrow 
bands  between  the  hepatic  parenchyma,  dissecting  apart  its 
columns  of  cells.     This  is  the  indication  of  the  cirrhosis. 

Under  a  higher  power  the  dark-colored,  homogeneous  patches 
show  themselves  to  be  composed  of  aggregated  cellular  elements 
with  nuclei  of  variable  form.  Some  of  these  are  elongated  and 
of  large  size  and  correspond  to  the  mononuclears ;  others  are 
smaller  and  many-lobed,  and  evidently  polynuclears.  The 
nuclei  are  in  the  condition  of  pycnosis,  that  is  to  say,  in  process 
of  degeneration,  and  show  only  as  blue  masses  of  chromatin 
without1  any  visible  finer  'structural  details.  The  protoplasm 
itself  is  not  altered,  but  the  cellular  outlines  are  distinguished 
with  difficulty.  These  cells  are  pus  cells,  formed  of  white  blood 
corpuscles  in  a  state  of  degeneration,  whose  aggregation  forms 
microscopic  abscesses.  At  the  edge  of  the  abscess  are  fine 
strands  of  young  connective  tissue. 

The  connective  tissue  islets  are  particularly  dense  in  the 
neighborhood  of  the  bile  ducts,  in  the  periportal  spaces.  The 
bile  canaliculi  have  a  lining  of  cuboidal  epithelium,  well  pre- 
served, though  in  the  center  of  some  of  them  there  may  be  a 
few  desquamated  cells  and  polymorphonuclear  leukocytes. 
About  the  bile  ducts  the  lesions  of  periangiocholitis  are  shown 
by  concentric  sheaths  composed  of  layers  of  connective  tissue 
and  inflammatory  collections  of  cells  of  blue  color.  In  this 
connective  tissue  are  many  pseudocanaliculi— false  bile  ducts— 
that  call  attention  to  themselves  by  a  double  layer  of  cells 
and  potential  but  not  distinct  lumina.  These  are  signs  of  endo- 
and  pericholangitis.  Occasional  collections  of  bile  pigment  in 
the  portal  connective  tissue  indicate  retention  of  bile.  The 

84 


columns  of  liver  cells  are  dissociated;    the  cells  here  and  there 
in  a  state  of  fatty  degeneration. 

Resume.— Multiple  abscess  of  the  liver,  of  which  the  biliary 
origin  is  shown  by  the  lesions  of  the  bile  canaliculi  (angiocholitis), 
by  the  retention  of  bile  and  the  periductal  sclerosis. 


Abscess. 


Fibrous 

reaction 

:    (sclerosis) 


Hepatic 
artery. 

Peri- 
portal 
sclerosis. 

Bile  duct. 

filled  with 

pus. 

Pseudo- 


bile  ducts. " 


Fig.  32.— Biliary  abscess  of  the  liver  with  cirrhosis. 
Stained  with  hematoxylon  and  eosin.     Magnified  30  diameters. 

Cirrhotic  liver  of  an  old  woman  "with  cholelithiasis.  The  organ 
was  crowded  with  little  abscesses  most  oj  which  were  visible  to  the 
naked  eye,  and  had  become  a  spongy  mass  filled  with  pus.  The 
drawing  shows  two  of  the  abscesses  surrounded  by  reactive  inflamma- 
tion (sclerosis),  and  columns  of  liver  cells  separate  and  compressed. 

85 


SECONDARY  CANCER  OF  THE  LIVER. 

Diagnosis  of  the  Organ.  — This  is  quite  easy  in  the  lower  part 
of  the  drawing  where  the  columns  of  liver  cells  show  distinctly. 

Diagnosis  of  the  Lesion. — An  examination  by  the  naked  eye 
or  with  a  low-power  lens  shows  distinct  masses  of  a  dark  color 
and  varying  size,  sharply  separated  from  the  more  pale  and 
uniform  part  of  the  section.  These  masses  are  composed  of 
epithelial  cells  often  arranged  in  the  form  of  glandular  acini. 
Some  narrow  strands  of  connective  tissue  carry  the  nutrient 
bloodvessels  of  the  tumor  and  at  the  same  time  its  stroma. 

Under  a  higher  magnification  the  nature  of  the  tumor  can 
be  better  made  out.  The  cells  are  columnar  and  arranged  in 
columns  or  acini.  The  nuclei  are  elongated  and  not  infrequently 
show  karyokinetic  figures,  indicating  abnormal  cellular  activity. 
Amorphous  matter  frequently  fills  the  spaces— products  of 
secretion.  The  cells,  both  by  grouping  and  structure  suggest 
those  of  a  glandular  mucosa  such  as  might  occur  in  some  part 
of  the  alimentary  canal— stomach  or  intestin. 

At  the  periphery  of  the  nodules  are  small  cellular  masses 
of  the  same  type  as  those  of  the  principal  tumor  which  is  thus 
shown  to  be  infiltrating  the  organ.  In  the  hepatic  paren- 
chyma itself  (far  to  the  right  and  low  down  in  the  drawing)  a 
mass  of  the  tumor  cells  (cancer  embolus)  can  be  seen  in  a  portal 
vein.  It  is  by  the  vessels  and  notably  by  the  portal  vein 
that  the  distribution  of  the  cancer  cells  takes  place. 

From  the  examination  of  this  section  one  quickly  grasps 
the  two  principal  and  most  important  features  of  malignant 
tumors:  the  destructive  invasion  and  the  metastasis,  char- 
acters that  joined  to  the  signs  of  cellular  activity  enable  one 
to  say  at  once  that  he  has  to  do  with  a  cancer. 

Is  it  a  primary  cancer  developed  on  the  spot  through  malig- 
nant transformation  of  the  columns  of  liver  cells,  or  bile  ducts, 
or  is  it  a  secondary  cancer? 

The  type  of  cells  found  does  not  suggest  hepatic  cells.  On  the 
contrary,  their  arrangement  in  glandular  acini  and  the  absence 
of  transition  between  the  hepatic  parenchyma  and  the  cancer 
make  us  incline  to  the  opinion  that  the  tumor  is  secondary. 

At  the  periphery  of  the  cancer  nodule  there  is  no  connective- 
tissue  separation  as  is  found  in  the  benign  tumors.  The  trabe- 
culae  are  compressed  and  reduced  to  thin  lamellae. 

86 


There  is  also  a  contingent  lesion  in  the  form  of  congestion 
that  chiefly  centers  about  the  central  veins. 

Resume. — Secondary  cancer  of  the  liver.  Cylindrical  epithe- 
lioma,  or  adenocarcinoma,  the  primary  seat  of  which  seems  to 
be  some  part  of  the  alimentary  canal. 


B 


Secondary 
cancer. 


Hepatic 
paren- 
chyma. 


Cancer 
nodules.  1 


A 


Lamin- 
ated 
appear- 
ance of 
the  col- 
umns of 
liver  cells. 


Cancer 
embolus. 

Columns 
of  liver 
cells. 


Fig.  33. — Secondary  cancer  of  the  liver. 


Stained  with  hematoxylon  and  eosin.     Magnified  90  diameters. 

Secondary  cancer  of  the  liver  characterized  by  the  occurrence 
of  numerous  tumor  nodules  secondary  to  cancer  of  the  pylorus. 

A. — Fragment  of  tissue  showing  numerous  nodules,  natural  size. 

B.— Periphery  of  one  of  the  nodules  shown  in  A  magnified  90 
diameters,  and  showing  the  hepatic  parenchyma  with  the  columns 
of  liver  cells  separated  and  compressed. 

87 


WALL  OF  AN  ECHINOCOCCUS  CYST  OF  THE 
LIVER. 

Diagnosis  of  the  Organ.— This  is  absolutely  impossible. 
There  is  no  liver  tissue  in  the  section  which  is  altogether  made 
up  of  a  pathological  new  formation.  For  the  diagnosis,  there- 
fore, we  must  depend  upon  information  obtained  from  the 
pathological  anatomical  clinic  where  the  specimen  was  obtained. 
This  informs  us  that  the  specimen  was  a  fragment  of  an 
echinococcus  cyst  of  the  liver. 

Diagnosis  of  the  Lesion. — The  upper  figure,  A,  shown  under 
a  low  magnification,  gives  the  general  topography  of  the  wall 
of  the  cyst.  In  the  interior  of  the  concavity,  turned  toward 
the  left,  there  is  nothing  more  than  debris  of  a  fibrinopurulent 
character.  Nothing  remains  either  of  the  membrane  or  of  the 
cyst  contents.  The  wall  of  the  cyst  consists  of  a  rather  thick 
composed  of  adult  fibrous  connective  tissue.  This  wall  repre- 
sents a  defensive  reaction  against  the  parasite  (echinococcus) 
formed  at  the  expense  of  the  connective  tissue  of  the  organ  in 
which  the  cyst  developed,  in  this  case  the  liver,  which,  as  has 
been  said,  is  not  visible  in  the  section. 

Under  a  higher  magnification  (see  B.)  the  structure  of  the 
wall  itself  is  shown.  That  which  should  at  once  strike  the 
observer  is  the  great  number  of  eosinophilic  cells  it  contains. 
These  are  polymorphonuclear  leukocytes  that  contain  great 
numbers  of  granules — acidophilic  granules — that  have  affinity 
for  acid  aniline  dyes  such  as  cosine.  Several  of  these  cells 
seem  to  contain  two  nuclei,  but  this  is  only  an  appearance 
that  results  from  the  close  approximation  of  cells  whose  limits 
cannot  be  accurately  defined.  Here  and  there  eosinophilic 
granules  may  be  seen  free  in  the  stroma. 

The  stroma  itself,  as  shown  in  the  drawing,  includes  a  capil- 
lary bloodvessel  and  connective-tissue  cells,  some  of  which  are 
elongated,  others  irregular— fixed  cells. 

The  intensity  of  the  local  eosinophilia  parallels  that  found 
when  the  blood  is  examined,  for  eosinophilia  is  almost  con- 
stantly found  in  parasitic  affections,  especially  in  cases  of  infesta- 
tion by  the  echinococcus.  In  this  very  case  the  eosinophiles 
in  the  circulating  blood  were  from  4  to  6  per  cent,  as  contrasted 
with  the  i  per  cent  which  is  supposed  to  be  normal. 

Resume.— Subacute  inflammatory  reaction  constituting  the 
wall  of  an  echinococcus  or  hydatid  cyst,  with  eosinophilia  both 
local  and  in  the  circulating  blood. 

88 


«9P  8  £&$$|  •      A 

>  W%   ^v 
&V**w -wsA   •      "/^-^ 

.>^  *  '    . ."  <-fcJV?  '  «v    .. 


Fibrous  wall   of 
the  cyst. 


Eosino- 
—  philic 
cells. 

_  Fibro 
blasts. 


Fig.  34.— Wall  of  a  hyatid  cyst. 
Stained  with  hematoxylon  and  eosin. 

A.— About  one-half  of  the  cyst  magnified  twice,  and  showing 
Us  wall  and  fibrinous  contents. 

B. — Part  of  the  wall  magnified  200  diameters,  and  showing  the 
great  number  of  eosinophilic  cells  it  contains. 

89 


SCLEROSIS  OF  THE  PANCREAS. 

Diagnosis  of  the  Organ.— Under  a  low-power  magnification 
the  parenchyma  of  the  organ  seems  to  be  formed  of  small 
masses  of  glandular  cells  disposed  about  a  potential  rather 
than  distinctly  visible  central  cavity.  The  finely  granular 
structure  of  the  protoplasm,  deeply  colored  by  the  hematoxylon, 
the  circular  arrangement  of  the  cells,  the  excentric  position  of 
their  nuclei  and  the  very  small  size  of  the  cavity  of  the  acini 
make  one  think  of  a  gland  in  full  activity  and  of  the  salivary 
gland  in  particular — parotid,  for  example.  But  upon  more 
careful  inspection  it  is  found  that  there  are  certain  small  pale 
areas  distributed  throughout  the  parenchyma— the  islands  of 
Langerhans.  In  these  one  finds  pale  or  dark  nuclei  distributed 
throughout  a  protoplasmic  mass  not  distinctly  divided  into 
cells— syncytial  or  plasmodial  mass. 

The  glandular  acini  plus  the  islands  of  Langerhans  enable 
the  diagnosis  of  the  pancreas  to  be  made.  The  acini  represent 
the  organ  of  external  secretion,  the  islands  of  Langerhans,  the 
organ  of  internal  secretion.  Between  these  two  formations 
there  are  various  intermediates  which  correspond  to  transition 
stages.  The  acini  can  transform  themselves  into  islands  of 
Langerhans  and  vice  versa.  In  the  interior  of  the  gland,  in 
the  substance  of  the  connective-tissue  partitions,  the  presence 
of  ducts  is  to  be  noted.  These  are  branches  of  the  ducts  of 
Wirsung  and  Santorini  and  are  composed  of  small  cubical  cells 
supported  by  a  dense  basement  membrane. 

Diagnosis  of  the  Lesion.— That  which  attracts  attention  is 
the  thickness  of  the  bands  of  connective  tissue  that  pass  through 
the  tissue  in  all  directions,  dividing  it  into  lobules.  There  are 
even  points  at  which  little  islands  of  the  acinous  tissue  are 
separated  from  the  main  mass  and  lost  in  the  substance  of  the 
connective-tissue  partitions.  Here  we  see  some  correspondence 
with  what  was  found  in  the  liver  in  Laennec's  cirrhosis;  but 
the  nature  of  the  parenchyma  differs. 

The  sclerosis  is  at  the  same  time  peri-  and  intralobular.  The 
large  bands  of  connective  tissue  divide  the  gland  into  lobules; 
the  finer  bands  of  the  same  tissue  penetrate  into  the  lobules 
and  dislocate  the  glandular  acini — periacinous  sclerosis,  and 
even  in  some  cases  monocellular  sclerosis. 

The  ducts  contain  a  number  of  desquamated  cells  which 
either  betray  the  inflammatory  nature  of  the  process,  or  may  be 
the  result  of  errors  in  fixation  and  treatment. 

Resume.— Chronic  inflammation  of  the  pancreas:  chronic 
sclerotic  pancreatitis. 

90 


Band  of  sclerotic 
tissue. 


Ducts. 


Ducts 

rounded 

by  sclerotic 

tissue. 


Glandular 
lobule. 


3  islands  of 
yLangerhans. 


Duct  of 
Wirsung. 


^ -Vessel. 

Fig.  35. — Chronic  pancreatis. 

Stained  with  hematoxylon  and  eosin.     Magnified  8  diameters. 

Sclerosis  of  the  pancreas  in  a  case  of  chronic  pancreatitis  con 
secutive  upon  cholelithiasis  in  an  old  man. 

91 


ADENOCARCINOMA  OF  THE  PANCREAS. 

The  section  shows  both  the  cancer  and  the  healthy  gland  and 
is,  therefore,  composed  of  two  distinct  parts  that  differ  in  their 
staining  qualities:  the  one  dark  colored  and  blue,  the  other  a 
great  deal  paler  and  more  rose  colored. 

Diagnosis  of  the  Organ.— In  the  upper  drawing  (Fig.  36,  A), 
the  dark  part  to  the  right  can  easily  be  recognized  as  pancreas 
because  of  the  presence  of  the  glandular  acini  and  the  island 
of  Langerhans. 

Diagnosis  of  the  Lesion.— To  the  left  in  the  same  drawing, 
in  the  pale-colored  area,  one  may  see  some  of  the  islands  of 
Langerhans  and  pancreatic  acini,  but  cannot  fail  to  be  struck 
by  the  disorderly  arrangement.  Instead  of  being  composed  of 
cells  regularly  arranged  about  a  central  cavity  there  are  long 
tubes,  more  or  less  attenuated,  with  a  lumen  scarcely  visible 
and  often,  indeed,  entirely  absent.  At  other  points,  on  the 
contrary,  the  central  cavity  may  be  very  obvious.  In  many  of 
the  dilated  acini  there  are  masses  of  finely  granular  material 
coagulated  by  the  reagents.  Finally,  and  this  is  most  charac- 
teristic, the  neoplasmic  cells  escape  into  the  stroma,  no  longer 
adopting  an  acinous  arrangement  and  resemble  the  fixed  con- 
nective-tissue cells  except  for  their  larger  size  and  more  spherical 
shape. 

Under  a  low-power  lens  the  tumor  seems  to  be  completely 
separated  from  the  normal  gland,  but  under  a  high  power  one 
is  surprised  to  find  at  various  points,  in  what  appears  to  be 
otherwise  normal  parenchyma,  some  areas  in  which  the  cells 
become  atypical,  show  the  same  appearance  as  in  the  tumor 
(zone  of  invasion)  and  reproduce  the  same  atypical  cellular 
arrangement  as  in  the  cancer  properly  so  called. 

Differential  Diagnosis. — Interstitial  pancreatitis  with  mono- 
nuclear  sclerosis  can  be  mistaken  for  cancer;  but  in  the  case 
before  us  the  difference  in  the  staining  properties,  the  almost 
perfect  preservation  of  the  normal  parenchyma  and  finally  the 
occurrence  of  occasional  cellular  monstrosities  make  us  throw 
aside  the  idea  of  simple  sclerosis  in  favor  of  cancer. 

The  dislocation  of  the  glandular  acini,  the  arrangement  of 
the  cells  in  tubules,  their  peculiar  staining  affinities,  which  all 
differ  from  the  normal,  enable  us  to  say  that  the  lesion  is  cancer 
of  the  pancreas  developed  from  the  cells  of  the  acini,  and  which 
has  in  some  places  reached  the  point  of  actual  infiltration. 

92 


Cancer. 


Pancreas 


Thickened 
connec- 
tive tissue 
partition. 


Cancer 

nests. 


Island  of 

Langer- 

hans. 


Invasion 

of  the 

stroma 

by  the 

cancer. 


B 

Atypical 
acinus. 


Acinus. 

Connec- 
tive 
tissue. 


Arteriole. 

Normal 

glandular 

acini. 

Island  of 

Langer- 

hans. 


Acinus 
with 

monstrous 
nuclei. 

Atypical 

cell 

formation 


Duct. 


Fig.  36. — Cancer  of  the  pancreas. 

Stained  with  hematoxylon  and  eosin. 

Fragment  removed  at  operation.  Death  shortly  after  followed 
from  obstruction  of  the  common  bile  duct. 

A.— Magnification  of  100  diameters,  showing  the  separation 
between  the  cancer  and  the  normal  pancreas. 

^.—Magnification  of  300  diameters,  showing  the  cancer  zone. 

93 


CHRONIC  PASSIVE  CONGESTION  OF  THE 
SPLEEN. 

Diagnosis  of  the  Organ.— To  the  naked  eye  the  section  is 
found  to  consist  of  a  pale  background,  distributed  over  which 
there  are  a  number  of  dark  points.  With  a  medium-power 
lens  the  background  is  found  to  be  composed  of  a  pale  tissue 
in  which  nuclei  and  red  blood  corpuscles  are  mixed  up.  The 
dark  points  are  found  to  be  masses  of  lymphoid  tissue,  nearly 
always  centered  about  a  small  bloodvessel — arteriole.  These 
are  the  Malpighian  bodies  characteristic  of  the  spleen.  The 
pale  substance  of  the  background  is  the  red  pulp;  the  dark 
points  and  the  Malpighian  corpuscles  the  white  pulp. 

A  greater  magnification  shows  a  Malpighian  corpuscle  in 
which  is  a  section  of  an  arteriole  near  the  periphery.  The 
cells  are  nearly  all  of  the  type  of  lymphocytes. 

Elsewhere  in  the  section  other  Malpighian  corpuscles  can 
be  found.  These  do  not  always  show  the  central  arteriole 
and  are  sometimes  entirely  without  the  vessel,  appearing  as 
lymphatic  ganglia  in  the  paler  background  of  splenic  pulp. 
Between  the  Malpighian  corpuscles  the  red  pulp  is  formed  of 
a  pale  tissue  in  which  various  elements  are  easily  recognizable. 
The  most  numerous  are  the  red  blood  corpuscles,  next  lympho- 
cytes, then  occasional  polymorphonuclear  leukocytes  and  cells 
with  budding  nuclei.  Finally,  separating  these  elements  there 
is  a  reticulum  comparable  to  that  seen  in  the  lymph  nodes. 

Diagnosis  of  the  Lesion.— In  the  section  itself,  the  red  pulp 
is  differentiated  from  the  white  pulp,  with  a  distinctness  that 
causes  the  Malpighian  corpuscles  to  stand  out  prominently. 
This  is  because  of  the  extreme  congestion  of  the  red  pulp  and 
the  consequent  predominance  of  the  red  corpuscles  over  the 
lymphocytes.  The  red  corpuscles  are  numerous  and  so  massed 
together  that  there  are  small  areas  of  actual  hemorrhage  in 
which  brownish  masses  of  blood  pigment — hematoidin — can  be 
distinguished.  Some  of  the  pigment  is  contained  in  the  interior 
of  large  cells — mononuclear  phagocytes. 

Attention  must  be  again  called  to  the  connective  tissue 
partitions— trabeculae— which  indicate  a  pronounced  sclerosis. 

Resume.— The  enormous  number  of  red  blood  corpuscles  in 
the  pulp,  the  presence  of  the  small  hemorrhagic  areas,  the 
numerous  collections  of  pigment  and  the  intensity  of  the  con- 
nective-tissue reaction  enable  the  diagnosis  of  chronic  passive 
congestion  of  the  spleen— cardiac  spleen— to  be  made. 

94 


Entire  section  magnified  twice. 


B 

Iron 

containing 

pigment 

(hemo- 

siderin) . 


Central 
arteriole. 


Capillary 


Red  pulp. 


White 
pulp. 


Malpighian  corpuscle  X  120. 


C        Red  pulp  X  450. 


Reticu- 
lum. 

Mesh  of 

the  retic- 

ulum. 

Mononu- 
clear. 


Pigment 
mass. 


Connec- 
tive 
tissue 
reticulum 


Malpig- 
hian cor- 
puscle of 
the   white 
pulp. 

Thickened 
connec- 
tive tissue 
trabecula 


Vessel. 


Lympho- 
cyte. 


Mononu- 

clear. 

Polymor- 

phonu- 

clear. 

Red  blood 
corpuscle. 


Fig.  37. — Chronic  passive  congestion  of  the  spleen,  in  an  old  man 
dying  of  asystole. 

95 


AMYLOID   INFILTRATION  OF  THE  SPLEEN. 
Sago  Spleen. 

The  spleen,  slightly  enlarged,  was  removed  from  a  patient 
dead  of  'chronic  pulmonary  tuberculosis. 

Diagnosis  of  the  Organ.— This  is  difficult  to  make  without 
examining  more  of  the  section  than  is  shown  in  the  drawing. 
By  so  doing  it  is  easily  possible  to  recognize  the  red  pulp  and 
locate  the  white  pulp,  some  of  which  is  not  changed  and  occurs 
as  typical  Malpighian  bodies  with  the  associated  arterioles 
and  the  numerous  fibromuscular  trabeculae. 

Diagnosis  of  the  Lesion.— To  the  right  of  the  drawing  is  a 
rounded  formation,  at  the  center  of  which  a  transverse  section 
of  an  arteriole  occurs.  The  presence  of  the  vessel  and  the 
rounded  shape  of  the  body  suggest  a  Malpighian  body,  but 
the  small  size  and  resemblance  to  the  surrounding  red  pulp 
show  that  if  it  be  such,  it  is  distinctly  pathological.  Moreover, 
instead  of  being  composed  of  lymphoid  cells,  it  is  largely  made 
up  of  masses  of  translucent  waxy  substance,  taking  a  pinkish 
color  with  the  eosin  stain.  These  are  amyloid,  a  conjugated 
proteid  composed  of  protein  and  condroitin  sulphuric  acid, 
deposited  between  the  cells  with  resulting  atrophy  and  dis- 
appearance of  many  of  them.  The  peculiar  shapes  of  the 
amyloid  deposits,  some  of  which  are  rounded,  some  sigmoid 
and  some  serpentine,  suggest  that  the  amyloid  substance,  as 
is  commonly  the  case,  has  first  infiltrated  about  the  walls  of 
the  capillaries  of  the  Malpighian  body. 

By  the  application  of  Lugol's  solution  to  amyloid  substance 
a  mahogany  red-brown  color  is  produced.  Gentian  violet  (i 
per  cent  aqueous  solution)  colors  amyloid  pink. 

Resume. — Deposits  of  homogeneous  waxy  substance  about 
capillary  vessels,  striking  characteristic  colors  with  iodine  and 
gentian  violet— amyloid  infiltration. 


96 


Amyloid 
substance. 

Artery  of 
the  Mal- 
pighian 
body. 


Splenic 
pulp. 


Fig.  38. — Amyloid  infiltration  of  a  malpighian  body  in  the  spleen. 
From  a  patient  dying  of  chronic  pulmonary  tuberculosis. 

Stained  with  hematoxylin  and  eosin.     Magnified  200  diameters. 


97 


TUBERCULOSIS  OF  THE  SPLEEN. 

Diagnosis  of  the  Organ. — The  spleen  can  be  recognized  by 
the  dark  dotting  of  the  Malpighian  corpuscles  upon  the  back- 
ground of  almost  homogeneous  paler  pulp  (Fig.  39,  A). 

Diagnosis  of  the  Lesion. — That  which  at  once  strikes  the 
observer  is  the  presence  of  four  or  five  spots  of  the  color  of 
"  dregs  of  wine,"  scattered  about  irregularly,  having  the  size 
of  millet  seeds  and  of  no  particular  shape.  Let  us  take  one 
of  these  and  subject  it  to  a  higher  power  for  more  careful  study 
(Fig.  39,  B). 

1.  At  the  right-hand  part  of  the  drawing,  at  a  part  correspond- 
ing very  nearly  to  the  center  of  one  of  the  spots  designated 
above,  we  see  an  amorphous  granular  tissue  in  which  minute 
nuclear  fragments  are  disseminated.     This  is  easily  recognized 
to  be  caseous  substance.    At  the  periphery  of  this  substance 
there  is  a  considerable  mass  of  a  black  pigment.     This  is  an 
artefact  and  results  from  the  action  of  bichloride  of  mercury, 
in  which  the  tissue  was  fixed,  upon  its  proteins. 

2.  To  the  left  of  this  caseous  zone  there  is  a  second  zone 
of  cells  of  the  type  known  as  epithelioid  cells.     They  have 
pale  protoplasm,  are  of  variable  shape  and  their  nuclei  are  not 
infrequently  elongated.     Between  them  are  occasional  giant 
cells. 

3.  Finally  there  is  a  third  zone,  at  the  extreme  left  of  the  draw- 
ing, in  which  appear  a  considerable  number  of  lymphocytes, 
grouped  about  a  central  point,  usually  corresponding  to  the 
position  of  an  arteriole.    In  these  one  recognizes  the  Malpighian 
corpuscles. 

The  rarity  of  the  element  often,  but  wrongly,  considered  to 
be  characteristic  of  tubercle — the  giant  cell — might  confuse  a 
beginner  as  to  the  tuberculous  nature  of  the  lesion.  But 
the  epithelioid  inflammatory  reaction,  added  to  the  intense 
and  precocious  caseous  transformation  and  the  tendency  to 
nodular  formation,  speak  only  in  favor  of  the  tuberculous 
nature  of  the  lesion. 

Resume. — From  the  histological  characteristics  it  may  be 
concluded  that  we  have  to  do  with  a  caseous  tuberculosis  of 
the  spleen,  but,  of  course,  it  requires  a  bacteriological  examina- 
tion and  the  demonstration  of  the  bacillus  to  confirm  the 
diagnosis. 


98 


,';••     Caseated 
8a    center. 

Giant  cell. 

Epitheli- 
oid  cell. 

Crystals 

§/'':.:     of  bichlo- 
ride of 
mercury 
(artefact) 


Masses  of  caseated 
tubercles. 


Fig.  39. — Tuberculosis  of  the  spleen. 

Stained  with  hematoxylon  and  eosin. 

Tuberculosis  of  the  spleen  in  a  woman,  aged  forty-five  years, 
dying  of  tuberculous  meningitis  following  pulmonary  tuberculosis 
with  cavity  formation. 

A.— Fragment  of  the  spleen  twice  natural  size,  showing  the 
distribution  of  the  lesions,  and  a  square  showing  the  area  from  which 
B  was  taken. 

B. — The  caseous  center  and  periphery  of  a  tuberculous  mass 
magnified  250  diameters. 


99 


TUBERCULOUS  LYMPH  NODE. 

Diagnosis  of  the  Organ.— To  the  naked  eye  or  under  a  low- 
power  lens  the  section  appears  oval  and  shows  at  one  of  its 
poles  a  greater  amount  of  pale  substance  than  at  the  other. 
The  lower  part  of  the  section,  seen  in  the  drawing  (Fig.  40), 
is  a  reticulated  lymphoid  tissue  composed  of  a  great  number  of 
small  deeply  staining  cells,  and  under  a  low  power  can  be  divided 
into  two  different  portions.  One  of  these,  below  the  capsule, 
sends  prolongations  into  the  depths  of  the  organ.  It  is  formed 
of  a  loose  tissue  composed  of  a  reticulum  poor  in  nuclei  and  is 
the  lacunar  substance.  The  other,  composed  of  cells  arranged 
in  dense  masses,  with  pale  centers — germinative  centers — is 
the  follicular  substance.  The  oval  shape  of  the  organ,  the 
presence  of  the  reticulated  and  follicular  substance  permits  the 
diagnosis  of  lymph  node.  The  differentiation  into  two  kinds  of 
substance— the  one  pale  and  lacunar,  the  other  dense  and 
follicular— ought  to  be  easily  recognized  by  the  student,  though 
beginners  frequently  mistake  the  pale  germinal  centers  of  the 
follicles  for  a  pathological  condition  and  suppose  the  node  to 
be  the  seat  of  secondary  cancer. 

Differential  Diagnosis. — Certain  lymphoid  organs  are  to  be 
distinguished  from  the  lymph  node: 

1.  The  spleen  is  recognized  by  the  presence  of  the  Malpighian 
corpuscles  which  are  lymphoid-cell  aggregations  in  the  center 
of  which  there  is  an  arteriole. 

2.  The  tonsils  can  be  recognized  by  the  squamous  epithelium 
that  covers  them  by  their  crypts  with  glands  and  by  the  absence 
of  any  connective- tissue  capsule. 

3.  The  thymus  is  recognized  by  the  absence  of  closed  follicles 
and  by  the  presence  of  the  corpuscles  of  Hassal  which  are 
characteristic. 

4.  The  appendix  is  easily  recognized  by  the  glandular  crypts 
and  the  presence  of  columnar  epithelium. 

Diagnosis  of  the  Lesion.  —In  the  upper  part  of  the  figure  the 
collection  of  pale-colored  areas  recalls  the  general  appearance 
of  the  miliary  tubercles  already  seen  in  other  sections,  especially 
the  lung.  The  caseous  centers  are  easily  found  and  there  are 
numerous  giant  cells  surrounded  by  coronets  of  epithelioid 
cells  with  the  usual  abundant  protoplasm,  large  pale  nuclei 
and  the  peripheral  zone  of  lymphocytes. 

Resume.—  Miliary  tuberculosis  of  a  lymph  node  in  an  early 
stage.  Later  this  might  terminate  in  suppuration  in  which 
one  would  find  nothing  but  a  central  caseous  mass  without 
structural  details  and  surrounded  by  a  fibrous  envelope. 

100 


.  Periganglionic  connec- 
jt  tive  tissue  capsule. 

r^pss^    Giant  cell  in  the 
M/jjfi'j-fr   center  of  miliary 
HI;  .tubercle. 


Lacunar 
substance. 


Fibro- 

fatty 

tissue. 


Lymph 
nodules 
with  germ- 
inative 
centers. 


3  normal 

lymph 

nodules. 


Lacunar 

substance. 


Fig.  40.  —  Tuberculosis  of  a  lymph  node. 
Stained  with  hematoxylon  and  eosin.     Magnified  16  diameters. 

An  iliac  lymph  node  removed  at  an  operation  upon  a  case  of 
ulcerative  tuberculosis  of  the  cecum.  The  lower  part  of  the  node 
is  normal  and  shows  the  lymph  nodules  with  germinative  centers; 
the  upper  part  contains  numerous  miliary  tubercles  with  giant  cells. 


101 


-  CANCER  .OF  A  LYMPH  NODE. 

Metastatic  Epithelioma,  Secondary  to  a  Cancer  of  the  Stomach. 

Diagnosis  of  the  Organ. — This  is  difficult  if  not  impossible  to 
make.  One  is  forced  to  have  recourse  to  information  from  the 
clinic  or  autopsy,  from  which  we  learn  that  the  structure  is  a 
lymph  node  from  the  lesser  curvature  of  the  stomach.  The  only 
indications  that  permit  us  to  suppose  the  structure  to  be  a 
lymph  node  are  the  presence  of  lymphoid  tissue  and  the  sur- 
rounding connective-tissue  capsule. 

Diagnosis  of  the  Lesion. — The  greater  part  of  the  section  is 
formed  of  cellular  aggregations,  pale  in  color,  with  insignificant 
masses  of  lymphoid  tissue  between  them.  In  this  case  it  is 
not  to  be  expected  that  one  could  separate  the  gland  into  its 
classical  elements,  lacunar  and  ganglionic.  We  have  to  do 
with  a  pathological  condition  of  some  special  nature,  as  the 
pale  areas  do  not  present  any  reticular  aspect,  but,  on  the 
contrary,  are  formed  of  cells  with  abundant  protoplasm,  dis- 
posed in  long  branching  processes  of  epithelial  cells — the  cancer 
nests. 

Under  a  higher  power  (Fig.  41,  B)  one  sees  all  of  the  cy to- 
logical  modifications  of  malignant  tumors;  budding  nuclei, 
often  multiple  in  the  same  cell;  numerous  and  often  atypical 
mitotic  figures,  etc.  The  arrangement  of  the  cells  is  anarchical, 
and  nothing,  apart  from  the  rough  draughts  of  acini,  suggests 
the  organ  from  which  the  cells  were  derived— atypical  epithe- 
lioma.  Nothing  but  their  epitheliomatous  character  is  recog- 
nizable. However,  in  other  cases  it  is  sometimes  possible  to 
find  in  the  secondary  tumors  in  lymphatic  nodes  an  arrangement 
of  the  cells  that  indicates  the  structure  of  the  organ  from  which 
the  cells  are  derived,  through  a  preservation  of  the  primitive 
arrangement  of  the  cells  as  in  the  original  organ. 

Resume.— We  have  to  do  with  an  epithelial  tumor  developed 
in  a  lymph  node,  that  is  to  say,  a  lymphatic  metastasis.  The 
cancer  cells  transported  by  the  currents  of  fluid  have  arrived 
in  the  lymph  node  where  they  have  grown  and  multiplied 
before  going  further.  The  arrangement  and  nature  of  the 
cancer  cells  here  is  very  atypical  and  does  not  permit  one  to 
say  from  what  organ  they  originally  came,  and  in  what  organ 
the  tumor  originally  started.  The  acinous  outlines,  however, 
suggest  it  to  be  from  a  glandular  organ.  To  make  sure,  it  is 
necessary  to  depend  upon  information  derived  from  the  autopsy 
or  from  the  clinic. 

102 


Connec- 
tive 
capsule. 

Follicular 
substance. 


,.  .<*  -^^^.. 


Cancer 

nest. 

Lymph 

nodule 

with 


Cancer 
nest 

suggesting 
an  acinus. 


Fig.  41. — Secondary  cancer  of  a  lymph  node. 
Stained  with  hematoxylon  and  eosin. 

The  node  was  removed  from  the  lesser  curvature  of  the  stomach 
in  a  case  of  cancer  of  the  pylorus. 

A.— Magnified  25  diameters,  and  showing  the  appearance  oj 
the  periphery  of  the  node. 

B.— Magnified  150  diameters,  and  showing  the  epithelial  cell 
masses  with  their  monstrous  cells. 

103 


CHRONIC  MYOCARDITIS. 
Fibrous  Plaques  on  the  Myocardium. 

Diagnosis  of  the  Organ.— If  a  section  of  the  wall  of  one  of 
the  ventricles  of  the  heart  be  examined  with  the  naked  eye, 
it  is  found  to  be  limited  on  the  external  surface  by  an  almost 
straight  line  and  on  the  internal  by  a  very  sinuous  one  with 
large  promontories  and  occasional  islets  wrhich  are  sections  of 
the  muscular  bundles. 

If  the  section  be  examined  with  low-power  lens  the  central 
portion  is  found  to  be  composed  of  the  muscular  tissue  of 
the  myocardium,  the  cells  of  which  are  easily  recognizable  by 
their  centrally  situated  nuclei  and  their  Y-like  branchings. 

If  we  now  turn  to  the  part  of  the  section  shown  in  the  draw- 
ing (Fig.  42)  we  see  that  at  its  superior  part  (A),  which  cor- 
responds to  its  external  surface,  the  myocardial  fibers  are  cov- 
ered with  a  thin  layer  of  adipose  tissue,  above  which  there  is 
a  thin  band  of  fibrillar  connective  tissue  which  is  the  visceral 
layer  of  the  pericardium— the  epicardium,  of  great  importance 
in  orienting  one's  self  in  studying  sections  of  the  heart. 

If  the  entire  thickness  of  the  section  was  shown  the  festooned 
line  with  its  promontories  and  islets,  which  corresponds  to  the 
endocardium,  would  be  at  the  bottom  of  the  drawing. 

Diagnosis  of  the  Lesion.— Here  and  there  strands  and  bands 
of  connective  tissue  penetrate  into  the  muscular  tissue  and 
separate  its  fibers.  They  appear  pale  rose  colored,  the  muscle 
being  distinctly  red.  The  connective  tissue  forms  considerable 
masses— the  fibrous  patches  of  the  myocardium— that  can 
be  distinctly  seen  with  the  naked  eye.  When  the  fibrous  tissue 
is  viewed  with  a  higher  magnification  it  is  found  to  be  com- 
posed of  collagenous  fibrillae,  with  some  cells  of  which  the 
nuclei  are  visible.  These  are  fixed  cells  of  the  connective 
tissue  and  betray  an  inflammatory  reaction.  Starting  from 
the  large  plaques,  the  fibrous  tissue  infiltrates  fasciculi  in 
bundles  of  varying  thickness — inter f as  cicular  sclerosis— and 
sometimes  even  between  the  cardiac  cells— inter  fibrillar  sclero- 
sis. Under  the  high-power  lens  the  myocardial  fibers  may 
show  degeneration;  they  become  pale,  the  protoplasm  becomes 
finely  granular  and  here  and  there  there  may  be  transverse 
fragmentation— segmentary  dislocation  of  the  fibers,  long  con- 
sidered to  be  characteristic  of  cardiac  degeneration,  but  now 
looked  upon  as  an  artefact  of  cadaverization.  Attention  must 
be  called  to  accumulations  of  pigment  granules  surrounding  the 
nuclei  of  the  cardiac  cells— pigmentary  degeneration. 

Resume.—  Chronic  myocarditis:  sclerosis  or  formation  of 
fibrous  patches  in  the  myocardium,  very  common  in  the  aged. 

104 


A 

Epicardium. 


Sub- 

epicardial 

adipose 

tissue. 


Myocardial 

fibers  cut 

transversely. 


Fibrous 
plaque. 


B 

Myocar- 
dial fibers 
cut  trans- 
versely. 


Inter- 
fascicular 
fibrous 
band. 


Myocar- 
diac  fibers 
cut  longi- 
tudinally. 


Fig.  42. — Chronic  myocarditis. 
Stained  with  hematoxylon  and  eosin. 

A  fibrous  plaque  in  the  right  -ventricle  of  the  heart  of  a  case  of 
Bright 's  disease. 
A. — Magnified  25  diameters. 
^.—Magnified  120  diameters. 

105 


COR  ADIPOSUM. 
Obese  Heart. 

Diagnosis  of  the  Organ.— Under  the  low  magnification  repre- 
sented in  the  drawing  this  is  scarcely  possible.  At  the  extreme 
lower  margin  the  section  passes  perpendicularly  through  a 
fibrous  and  vascular  membrane  which  is  the  epicardium. 
Ascending  from  this  we  reach  a  thick  layer  of  adipose  tissue 
containing  a  vessel,  and  above  this,  beginning  at  about  the 
middle  of  the  drawing  there  appear  irregularly-shaped  aggre- 
gations of  red  dots,  while  in  the  upper  third  of  the  section 
there  are  groups  of  horizontal  wavy  red  lines. 

Employing  a  higher  magnification  these  latter  can  be  resolved 
into  bundles  of  transversely  striated  muscle  fibers,  made  up  of 
quadrilateral  segments  with  centrally  situated  nuclei  and  lateral 
anastomoses  by  which  the  cardiac  muscle  can  at  once  be  recog- 
nized, and  the  tissue  diagnosed  as  the  heart. 

Diagnosis  of  the  Lesion. —Three  things  should  at  once 
impress  the  student  as  peculiar:  (i)  The  large  quantity  of 
adipose  tissue;  (2)  its  distribution  among  the  muscle  bundles 
and  fibers;  (3)  the  small  size  of  the  muscle  fibers. 

The  heart  was  removed  from  an  obese  individual  who  suffered 
from  shortness  of  breath  upon  exertion.  The  microscopic 
findings  explain,  at  least  in  part,  the  symptoms  mentioned. 
The  increase  in  the  subepicardial  adipose  tissue  and  its  descent 
between  the  muscle  bundles  and  fibers  has  separated  them 
so  as  to  interfere  with  conjoint  action  and  diminish  their  power, 
as  well  as  compressing  them  so  that  many  of  them  atrophy — 
i.  e.,  become  smaller  in  size. 


106 


Separated 
and  atro- 
phic  mus- 
cle cell  in 
longitud- 
inal sec- 
tion. 

Separated 
and  atro- 
phic  mus- 
cle cell  in 
transverse 
section. 

Fat  cells. 
Vessel. 


Epicar- 
dium. 

Fig.  43. — Cor  adiposum — adipose  heart.  Heart  suffering  from  fatty 
infiltration  of  the  intermuscular  connective  tissue,  with  resulting  sepa- 
ration and  atrophy  of  the  muscular  fibers. 

Magnified  25  diameters. 


107 


ACUTE  FIBRINOUS  PERICARDITIS. 

Diagnosis  of  the  Organ.— The  section,  as  seen  in  the  drawing 
(Fig.  44)  is  composed  of  two  compact  lamina,  bound  together 
by  a  loose  tissue  of  very  atypical  appearance.  At  the  extreme 
inferior  portion  the  fibers  of  the  myocardium,  with  their  central 
nuclei  can  be  recognized.  Covering  the  myocardium  there  is 
a  thin  layer  of  adipose  tissue  between  it  and  a  thick  fibrous 
band— the  pericardium.  The  presence  of  these  structures 
enables  us  to  recognize  the  outer  surface  of  the  heart. 

Diagnosis  of  the  Lesion.— In  the  lower  part  of  the  drawing, 
in  the  adipose  tissue,  there  are  some  large  vessels,  about  which 
are  collections  of  small  cells.  The  epicardial  layer  is  reduced 
to  the  condition  of  granulation  tissue,  a  type  of  inflammatory 
tissue  with  dilated  capillaries  and  lymphocytes,  of  which  the 
whole  forms  a  dark  layer  above  the  subepicardial  adipose 
tissue.  The  endothelium  limiting  the  pericardium  is  replaced 
by  a  fine  fibrillar  tissue  which  takes  the  red  color  of  the  eosin 
with  avidity — this  is  fibrin. 

The  extreme  upper  edge  of  the  drawing  represents  the  parietal 
layer  of  the  pericardium.  It  is  formed  of  parallel  bands  and 
fasciculi  of  connective  tissue,  accompanied  by  vessels  and 
nerves.  At  its  middle  portion  one  finds  granulation  tissue  and 
infiltration  comparable  to  that  in  the  epicardium.  The  endo- 
thelium of  the  parietal  layer,  like  that  of  the  visceral  layer 
has  given  place  to  a  fibrinous  exudate.  Between  the  two 
principal  structures  in  the  drawing— the  epicardium  and  the 
pericardium — and  binding  them  together,  there  is  a  broad 
zone  of  lamellar  tissue  formed  of  fibrillae  with  a  few  nuclei. 
These  are  false  membranes  of  fibrin.  At  certain  points  the 
fibrin  is  organizing  as  is  shown  by  the  appearance  of  a  few 
new  vessels.  The  organization  is,  however,  only  beginning  as 
the  patient  died  of  the  pericarditis  before  permanent  adhesions 
had  time  to  form. 

Resume. — Acute  fibrinous  pericarditis.  Information  derived 
from  the  bacteriological  laboratory  showed  that  the  disease 
was  caused  by  the  pneumococcus. 


108 


Layer  of  vascular 
connective  tissue. 

Granulation 
tissue. 


Fibrin  undergo- 
ing organization. 


Fibrin. 

Epicardium. 

Subepicardial 

layer  of  adipose 

tissue. 

Vessel  with  peri- 
vascular  infiltra- 
tion. 


Fibrous 
sac  of  the 
pericar- 
dium. 


Fibrinous 
exudate. 


Epicard- 
ium and 
sub-epi- 
cardial 
tissue. 


Myocar- 
dium. 


Fig.  44. — Acute  fibrinous  pericarditis. 
Stained  with  hematoxylon  and  eosin.     Magnified  10  diameters. 

Pneumococcic   acute   serofibrinous   pericarditis   with    resolving 
exudate. 

109 


ULCERO-VEGETATIVE  ENDOCARDITIS. 

Diagnosis  of  the  Organ. — The  section  can  easily  be  recog- 
nijzed  as  the  wall  of  the  heart  by  the  features  already  pointed 
out.  By  knowing  the  normal  thickness  of  the  ventricular  walls 
it  can  easily  be  guessed  that  the  section  includes  the  entire 
cardiac  wall.  Three  portions  are  selected  for  special  examina- 
tion and  are  indicated  by  the  three  small  rectangles  shown  in 
the  drawing  (A). 

Diagnosis  of  the  Lesion.— To  facilitate  the  examination  the 
selected  portions  will  be  considered  from  above  downward. 

1.  The  peripheral,  or  epicardial  portion  (Fig.  45,  B). 
Passing  from  the  outer  portion  of  the  section  toward  the 

deeper  tissues,  we  find  first  the  epicardium,  a  dense  fibrillar 
tissue  of  considerable  thickness.  Below  it  there  is  a  layer  of 
adipose  tissue  and  below  it  the  muscle  of  the  myocardium. 

The  only  abnormality  is  the  presence  in  the  adipose  and 
muscular  tissues  of  a  considerable  number  of  inflammatory 
small  round  cells. 

2.  The  central  or  myocardial  portion  (Fig.  45,  C), 

In  this  one  sees,  at  once,  the  presence  of  strands  of  dense 
homogeneous  connective  tissue— plaques  and  bands  of  fibrous 
myocarditis.  To  the  left  in  the  drawing  there  is  an  arteriole 
with  a  very  thick  wall.  Above  and  to  the  right  the  fibers  of 
the  myocardium  are  dissociated  and  separated  from  one  another 
by  fine  bands  of  sclerosis.  Examination  with  a  high  power  may, 
in  well-fixed  and  prepared  tissues,  permit  the  various  stages  of 
the  muscular  degeneration  to  be  made  out.  They  are  charac- 
terized by  a  homogeneous  staining  of  the  protoplasm,  dis- 
appearance of  the  striae  and  of  the  nucleus,  etc. 

3.  The  part  shown  in  Fig.  45  (D)  corresponds  to  the  endo- 
cardial  surface.     As  the  surface  is  approached  the  entire  tissue 
is  found  to  be  infiltrated  with  cells  of  various  types:    lympho- 
cytes, mononuclears  and  polymorphonuclears.     The  last-men- 
tioned are  rather  rare.     At  the  extreme  lower  portion  of  the 
section,  the  lower  ragged  edge  in  the  drawing,  the  color  becomes 
dark   blue.     This   is   granulation   tissue   in   which   numerous 
mononuclear  and   polymorphonuclear   cells  well   advanced  in 
degeneration  can  be   seen.     There  are  also  numerous  small 
reddish  bands  with  a  finely  fibrillar  appearance  composed  of 
fibrinous  exudate.    All  of  the  endothelial  covering  has  dis- 
appeared, and  the  lesion  forms  a  true  ulceration. 

Resume.— A  cute  ulcerative  endocarditis.  The  section  shows 
the  ventricular  wall  of  the  heart,  in  which  the  disturbance 
is  almost  limited  to  the  endocardial  surface. 

110 


Epicar- 
dium. 


B 

Visceral 
layer  of 
the  peri- 
cardium. 


Sub-epi- 

cardial 

layer  of 

fibrous 

and 

adipose 

tissue. 


Myocar- 
dium. 


Endo- 
cardium. 


c 

Myocar- 
dial 

bundles 
under- 
going 
sclerosis. 


Arteriole.  -  f1 


Connec- 
tive 
tissue. 
Hyper- 
plastic 
myocar- 
dial 
bundle. 


Ulcerated 
and  necro- 
tic  endo- 
cardium. 


Fig.  45. — Ulcero-vegetative  endocarditis. 

Stained  with  hematoxylon  and  eosin. 

Entire  thickness  of  the  ventricular  wall  twice  magnified,  with 
small  rectangles  showing  where  fragments  B,  C  and  D  were  taken 
for  further  examination. 

Ill 


FATTY  DEGENERATION  OF  THE  HEART  MUSCLE. 

The  section  is  a  longitudinal  one  passing  through  the  wall  of 
the  heart  of  a  case  of  ''tabby-mottling,"  occurring  in  pernicious 
anemia. 

Diagnosis  of  the  Organ.— This  should  not  be  difficult.  The 
tissue  is  composed  of  longitudinal  bundles  of  a  fibrillar  structure 
with  distinct  longitudinal  and  transverse  striations  (not  shown 
in  such  distinctly  diseased  parts  as  that  selected  for  the  drawing). 
It  is  also  composed  of  irregularly  quadrilateral  segments  that 
can  be  recognized  as  cardiac  muscle  cells,  both  by  the  occasional 
anastomosing  fasciculi  and  the  centrally  placed  nuclei. 

Diagnosis  of  the  Lesion. — Examination  under  a  high  mag- 
nification shows  that  in  many  of  the  fibers  the  original  trans- 
versely striated  fibrillar  structure  and  the  nuclei  have  dis- 
appeared, and  in  their  place  are  collections  of  granules  which 
are  colored  black  with  the  osmic  acid.  These  are  fatty  drop- 
lets, the  result  of  the  degeneration  of  the  muscle  following 
malnutrition  or  intoxication.  Their  presence,  together  with 
the  degenerative  changes  with  which  they  are  associated, 
explains  the  yellow-^gray  speckled  appearance  of  the  wall  of 
the  heart. 

Resume. —Fatty  degeneration  of  the  muscle  fibers  of  the 
ventricular  wall— /o#3>  degeneration  of  the  heart. 


112 


Muscle 
nucleus. 


Fatty 

granules 

stained 

black  by 

osmic 

acid. 


Fig.  46. — Fatty  degeneration  of  the  heart  muscle.     From  a  case  of 
pernicious  anemia. 

Stained  with  osmic  acid.      Magnified  75o"diameters. 


113 


OBLITERATIVE  ENDARTERITIS. 
Endarteritis  Obliterans. 

Diagnosis  of  the  Organ.— The  section  is  of  a  tube  whose  wall 
is  divisible  into  an  external  zone  that  stains  a  deep  red— tunica 
media — and  an  internal  zone  of  paler  color — tunica  interna — 
separated  by  a  thin  undulating  membrane,  the  internal  limiting 
membrane,  a  landmark  important  both  in  making  the  diagnosis 
of  the  organ  and  of  the  lesion.  Outside  of  this  elastic  limiting 
membrane  the  unstriated  muscular  fibers  can  be  recognized  by 
their  elongated  nuclei.  To  bring  out  the  elastic  fibers  recourse 
must  be  had  to  staining  by  one  of  the  specific  stains  of  Mallory 
or  Weigert,  or  the  orcein  stain.  In  the  lumen  of  the  tube 
there  are  a  number  of  red  blood  corpuscles  that  confirm  the 
suspicion  that  the  tube  is  a  bloodvessel.  The  external  tunic, 
the  adventitia  lacking  in  this  section,  being  represented  only 
by  the  connective  tissue  forming  the  stroma  of  the  organ  in 
which  the  vessel  was  contained.  The  distinctness  of  the 
undulating  membrane  shows  that  the  vessel  is  an  artery;  in 
this  case  a  visceral  artery  of  middle  size. 

Diagnosis  of  the  Lesion.— The  inner  coat  is  very  thick. 
Instead  of  being  composed  of  an  endothelium  with  a  thin  layer 
of  subjacent  connective  tissue,  it  has  undergone  an  enormous 
thickening  through  hyperplasia  of  the  tunic  beneath  the  endo- 
thelium which  forms  a  very  thick  stratified  connective  tissue, 
with  occasional  elongated  nuclei,  particularly  numerous  in  the 
neighborhood  of  the  lumen.  In  proportion,  as  we  remove  from 
the  lumen  toward  the  muscular  coat,  the  nuclei  little  by  little 
lose  their  staining  properties  and  become  as  pale  as  the 
surrounding  tissue.  The  connective  tissue  of  the  endarterium 
becomes  structureless,  colorless  and  devoid  of  fibrillar  structure— 
hyaline  degeneration — which  frequently  complicates  areas  of 
endarteritis  in  the  visceral  vessels,  as  well  as  occurring  in 
atheromatous  degeneration  of  the  aorta  and  great  peripheral 
arterial  vessels. 

The  tunica  media — the  musculo-elastic  tunic — does  not  show 
any  notable  alterations.  The  lumen  of  the  artery,  though 
diminished  in  size  is  not  yet  closed. 

Resume.  — Arteritis  chiefly  confined  to  the  internal  tunic, 
hence  endarteritis,  and  with  a  tendency  to  obliteration. 


114 


Greatly 
thickened 
internal 
tunic. 
Lumen  of 
the  artery 
with 
blood. 
Fraying 
out  of  the 
internal 
coat  (arte- 
fact) 


Fig.  47. — Endarteritis  obliterans. 


Periarte- 
rial  tissue 
(sclerosed 
kidney) . 

Median 
musculo- 
elastic 
tissue. 

Internal 
limiting 
mem- 
brane. 


Vessel  of 
the  renal 
paren- 
chyma. 


Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

Section  of  an  artery  in  the  kidney  of  a  case  of  chronic  interstitial 
nephritis  with  pronounced  vascular  lesions.  The  great  thickening 
of  the  inner  coat,  inside  of  the  festooned  line  of  the  internal  limiting 
membrane,  effecting  an  incomplete  obliteration  of  the  lumen  of  the 
vessel,  is  to  be  carefully  noted. 


115 


ENDARTERITIS  OBLITERANS. 

Stained  with  Orcein. 

Diagnosis  of  the  Organ.— Again  we  have  to  do  with  a  trans- 
verse section  of  a  cylindrical  tube,  slightly  flattened  and  having 
a  lumen  that  is  slightly  excentric.  The  drawing  A  represents 
one-half  of  the  entire  section.  At  first  glance  it  is  difficult  to 
make  a  diagnosis  of  the  organ  because  of  the  special  method  of 
staining  adopted  (orcein);  nevertheless,  the  circular  character 
of  the  organ,  the  absence  of  epithelium  and  of  lymphoid  tissue, 
and  above  all  the  presence  of  the  sinuous  blue-black  line — 
elastica— permit  one  to  recognize  an  artery.  The  sinuous  line 
pointed  out  is  nothing  more  than  the  internal  elastic  limiting 
lamina  separating  the  endarterium  from  the  mesarterium. 
The  elastic  fibers  become  more  and  more  thick  until  they  form 
a  dense  feltwork.  They  consist  of  long  black  filaments  running 
parallel  with  one  another  and  showing  distinct  undulations. 

Diagnosis  of  the  Lesion.— There  are  no  notable  disturbances 
in  either  the  external  or  middle  tunics.  All  of  the  pathological 
alterations  take  place  inside  of  the  internal  limiting  elastics, 
that  is  to  say,  in  the  endarterium.  Instead  of  consisting  of 
an  endothelial  layer  superimposed  upon  a  thin  layer  of  con- 
nective tissue,  as  can  be  seen  in  the  right-hand  lower  corner  of 
the  drawing  (Fig.  48,  A),  it  has  undergone  enormous  thickening 
in  the  form  of  a  hyperplasia  of  the  subendothelial  fibrillar  layer. 
At  certain  points,  and  especially  at  the  internal  limiting  elastic 
membrane,  the  endarterium  assumes  a  pale  areolar  and  frag- 
mented appearance— hyaline  degeneration  corresponding  to  the 
beginning  of  the  formation  of  an  atheromatous  area  (Fig.  48,  B). 

The  lumen  of  the  artery  is  extremely  diminished  and  seems 
to  have  undergone  an  excentric  displacement.  This  appear- 
ance is  due  to  the  fact  that  the  plaque  of  endarteritis  does  not 
extend  all  around  the  vessel.  The  lumen  still  permits  the 
passage  of  blood,  but  it  is  so  reduced  that  except  for  the  anas- 
tomotic  branches,  the  territory  of  its  distribution  is  menaced 
by  ischemic  gangrene. 

Resume1.  —  Endarteritis  obliterans  of  the  superior  mesenteric 
artery.  It  resulted  in  an  infarct  of  the  intestine  and  the  death 
of  a  woman  aged  seventy  years. 


116 


Point  represented  in  Fig.  B 


Adventitia  . 
Elastic  fibers 
of  the  tunica         £ 
media.  — 


Muscle 

fibers  of 

the  tunica 

media. 


Internal 
limiting 
mem- 
brane. 


Disso- 
ciated 
elastic 
fibers  of 
the  mesar- 
terium. 


Elastic 
layer. 


Muscle 
fibers. 


Entire 
section 
X  70. 

Thick- 
ened 
endarter- 
ium  with 
hyaline 
degenera- 
tion; 

beginning 
atheroma 


B 

Magnified 

ISO 

diameters . 

Internal 

elastic 

layer. 


Sub- 
endothe- 
lial  fibrous 
tissue. 


Fig.  48. — Endarteritis  obliterans. 

Stained  with  orcein. 

Partly  obliterated,  superior  mesenteric  artery  of  a  woman  aged 
seventy  years. 

117 


ARTERIAL  ATHEROMA. 

Diagnosis  of  the  Organ. — One  can  recognize  the  organ  as  a 
fragment  of  the  wall  of  a  large  vessel  of  which  the  middle  tunic 
is  formed  of  muscle  and  elastic  fibers  (the  elastic  fibers  are 
not  visible  in  this  case  because  the  specimen  has  not  been  a 
appropriately  stained)  without  a  distinct  internal  limiting 
membrane.  Such  a  structure  is  characteristic  of  the  aorta  or 
pulmonary  artery.  The  external  tunic  is  composed  of  a  loose 
connective  tissue  containing  a  number  of  vessels,  though  the 
middle  and  internal  tunics  contain  none. 

Diagnosis  of  the  Lesion. — In  Fig.  49,  A,  the  lower  drawing, 
if  one  follows  the  section  from  left  to  right,  he  finds  a  certain 
point  at  which  the  inner  tunic  seems  to  separate  from  the 
middle  one,  and  the  endarteritis  assumes  greater  and  greater 
importance.  From  inside  out,  that  is  to  say,  from  below 
upward,  one  notes  the  presence  of  an  unaltered  endothelium, 
an  inner  tunic  slightly  thickened,  but  of  a  colorless  necrotic 
appearance,  passing  into  the  principal  lesion— the  area  of 
arteriosclerosis— which  is  subjacent. 

This  area  is  composed  of  a  pale  zone  of  friable  appearance  in 
which  there  are  elongated  spindle-shaped  crystals  of  fatty 
acids,  and  perhaps  some  lozenge-shaped  crystals  of  cholesterin. 
These  crystals  have  been  subjected  to  the  action  of  various 
reagents— alcohol,  xylol,  etc.,  in  the  course  of  the  preparation 
of  the  section,  and  nothing  is  now  left  but  the  spaces  in  which 
the  crystals  were  originally  contained.  Besides  the  crystals 
which  prove  the  presence  of  fatty  degeneration  of  the  deeper 
layers  of  the  intima,  some  much-altered  leukocytes  (macro- 
phages) ,  some  globules  of  fat  and  above  all  some  bluish  masses 
which  indicate  the  beginning  of  calcareous  infiltration  are  still 
to  be  found  in  the  area. 

The  internal  tunic  separating  the  area  from  the  lumen  of 
the  vessel  is  very  much  thinned,  and  almost  ready  to  rupture 
and  liberate  the  contents  of  atheromatous  swelling  into  the 
torrent  of  the  circulation.  Outside  of  the  atheromatous  area 
(above  in  the  drawing)  one  notes  the  integrity  of  the  middle 
coat  of  the  artery.  It  is  with  difficulty  that  one  sees  the  dis- 
appearance of  some  of  the  smooth  muscular  fibers  separated 
by  hyaline  tissue  (tiger  appearance  of  the  mesarterium) . 

Finally,  the  adventitia  (not  visible  here)  is  intact  and  the 
vasa  vasorum  are  normal. 

Resume. — Chronic  arteritis  with  atheromatous  degeneration 
such  as  one  often  sees  at  the  source  of  one  of  the  larger  branches 
of  the  aorta — arterial  atheroma. 

118 


Newly 
formed 
vessels. 


Tunica  media. 
Atheromatous  focus. 
Tunica  interna. 

Fig.  49.— Atheroma  of  an  artery. 

Section  of  the  wall  of  an  atheromatous  abdominal  aorta  of  an 
old  man. 

A.— General  mew  of  the  specimen  twice  natural  size.  The 
portion  between  the  vertical  lines  on  the  right  side,  is  that  selected 
for  higher  magnification  in  B. 

E.—  This  shows  an  atheromatous  focus  with  crystals  of  fatty 
acids  and  plates  of  cholesterin.  It  is  limited  above  by  the  middle 
tunic,  below  by  the  internal  tunic.  The  external  tunic  does  not 
show,  having  been  torn  off  in  removal  of  the  tissue  at  the  autopsy. 


119 


CALCIFIED  ARTERY. 

This  is  a  common  affection  of  the  peripheral  arteries  of 
elderly  people  and  may  occur  independently  of  endarteritis  or 
in  association  with  it.  It  is  most  common  in  the  arteries  of 
the  extremities,  but  this  particular  section  is  from  the  cancerous 
breast  of  an  old  woman. 

Diagnosis  of  the  Organ.— The  greater  part  of  the  section 
consists  of  a  tissue  whose  architecture  bears  no  correspondence 
to  that  of  any  normal  structure  of  the  body  and  therefore  may 
not  be  within  the  knowledge  of  the  student.  It  is  cancer  or 
carcinoma,  and  with  it  we  have  nothing  to  do  at  present. 

That  which  concerns  us  now  is  the  striking,  dark-blue  struct- 
ure that  occupies  the  greater  part  of  the  center  of  the  drawing 
and  forms  a  circle  with  an  irregular  central  opening.  It 
impresses  one  as  a  section  of  some  tubular  structure.  It  is 
bounded  externally  by  concentrically  arranged  parallel  con- 
nective-tissue fibers,  which  as  one  advances  toward  the  center, 
here  and  there,  in  the  better-preserved  parts,  abut  against 
unstriated  muscle  cells.  The  central  opening  is  limited  by  a 
thin,  flattened  cellular  structure— endothelium.  A  brief  re- 
flection enables  the  student  to  recognize  the  adventitia,  the 
media  and  the  intima  of  a  bloodvessel,  and  taking  into  con- 
sideration the  thickness  of  the  middle  coat  to  diagnose  an  artery. 

Diagnosis  of  the  Lesion.— In  the  upper  part  of  the  sketch, 
when  the  wall  of  the  artery  is  least  affected  and  when  the  lesion 
is  probably  youngest— it  will  be  seen  that  the  middle  coat  is 
the  chief  seat  of  disturbance,  and  is  partly  replaced  by  masses 
of  dark  blue,  at  certain  points  in  which  there  are  colorless 
deposits  of  a  highly  refracting,  crystalline  substance.  This  is 
of  calcine  nature  and  constitutes  calcification  of  the  middle  coat 
of  the  vessel.  The  calcareous  material  when  crystalline  remains 
uncolored;  when  amorphous,  absorbs  the  hematoxylon,  and 
as  it  increases  the  alkalinity  of  the  adjacent  muscular  tissue 
causes  it  also  to  absorb  the  hematoxylon  so  that  all  about  the 
mineral  deposits  the  tissue  becomes  intensely  dark  blue  in 
color. 

In  the  lower  part  of  the  section  of  the  vessel  a  much  greater 
deposit  occurs,  distending  the  tissue  so  as  to  make  it  encroach 
upon  the  lumen  which  is  diminished  in  consequence.  At  this 
point  it  is  impossible  to  say  that  there  may  not  have  been 
endarteritis  in  association  with  the  medium  calcification,  and, 
indeed,  the  two  processes  not  infrequently  occur  in  the  same 
vessels,  though  they  are  independent  of  one  another. 

120 


Such  changes  in  the  arterial  walls  makes  them  inelastic, 
brittle  and  subject  to  traumatic  injury  and  rupture,  as  well 
as  diminishing  their  conducting  powers.  The  parts  supplied 
by  such  arteries  are,  therefore,  apt  to  fall  into  a  state  of  mal- 
nutrition, and  in  the  case  of  the  extremities  of  the  body  into 
senile  gangrene.  Naturally  the  danger  is  greater  when  the 
calcification  of  the  middle  coat  is  accompanied  by  endarteritis 
by  which  the  the  lumen  is  further  obstructed  and  the  conducting 
power  of  the  vessel  further  diminished. 

Resume.— Calcification  of  the  middle  coat  of  the  artery— 
a  condition  which,  when  extreme  and  widespread,  gives  rise 
to  the  condition  often  described  as  "pipe-stem"  arteries. 


Vein. 


Group  of 
—  cancer 
cells. 

_  Intima. 

Lumen  of 
artery. 

_  Calcified 
media. 

Adventi- 
tia. 


Fig.  50. — Calcified  artery.  The  artery  occurs  in  a  mammary  gland 
almost  completely  destroyed  by  carcinoma.  The  disease  of  the  vessel 
wall,  however,  is  independent  of  the  tumor  and  probably  antedates  it. 

Stained  with  hematoxylin  and  eosin.      Magnified  50  diameters. 


121 


OBLITERATIVE  PHLEBITIS. 
Phlegmasia  Alba  Dolens. 

Diagnosis  of  the  Organs.— The  section  is  of  a  tube  with  its 
wall  and  contents  (Fig.  51,  A).  The  smooth  muscular  and 
elastic  fibers  in  the  wall  form  a  ring  of  considerable  density, 
lined  on  the  inside  with  a  pale  edging  and  on  the  outside  by  a 
cellular  layer,  showing  that  in  all  probability  we  have  to  do 
with  a  vessel.  The  thinness  of  the  wall,  the  absence  of  an 
internal  elastic  limiting  membrane,  make  us  suspect  that 
the  vessel  is  a  vein.  Compare  it  with  the  section  of  the  artery 
shown  in  drawing  (Fig.  45). 

Diagnosis  of  the  Lesion.— The  lumen  of  the  vessel  is 
obstructed  by  a  clot— thrombosis  (Fig.  51,  B). 

In  following  the  wall  of  the  vein  from  outside  inward  we 
encounter  the  following: 

1.  The  adventitia,  or  external  tunic,  a  loose  cellular  tissue 
with  numerous  vessels.     There  are  no  alterations  here  apart 
from  a  mild  inflammatory  infiltration  suggesting  a  deeper  lesion. 

2.  The  middle  tunic,  musculo-elastic,  of  comparative  thin- 
ness also  seems  to  be  intact.     It  does  not  show  the  mottled 
appearance  of  chronic  arteritis. 

3.  The  internal  tunic,  on  the  contrary,  shows  important  altera- 
tions in  all  points  comparable  to  those  of  chronic  endarteritis 
(thickening  of  the  connective   tissue  layers).     However,   the 
inflammatory  process  is  a  great  deal  more  acute  and  terminates 
in  the  formation  of  a  clot  that  obstructs  the  lumen  of  the 
vessel.     The  lesion  of  the  wall  of  the  vessel  has  produced  the 
clot    (thrombosis).     The    venous    endothelium    resting    upon 
stratified  subendothelial  connective  tissue  has  disappeared  and 
the  internal   tunic  is  continuous  with  the  thrombus. 

The  latter  is  formed  by  red  blood  corpuscles  still  distinct, 
and  by  bands  of  fibrin  containing  inflammatory  cells  in  the 
meshes. 

The  center  of  the  thrombus  has  become  fragmented  in  the 
course  of  treatment  with  the  reagents  and  the  form  of  the  rent, 
the  distinct  lines  of  the  openings,  and  the  absence  of  red  blood 
corpuscles  show  their  artificial  nature. 

Resume.— Obliterating  or  thrombosing  phlebitis,  commonly 
observed  in  phlebitis  of  the  limbs — phlegmasia  alba  dolens. 


122 


Fibrin 
and 
inflam- 
matory 
cells. 


Tunica  externa 
Tunica  media., 

Tunica  interna.- 


Clot. 


Clot. 


Lacerated 
internal 
coat 
(artefact) 


Middle 
coat. 


Peri  vas- 
cular 
tissue. 


Fig.  51. — Obliterative  phlebitis. 
Stained  with  hematoxylon  and  eosin. 

A. —  Transverse  section  of  the  femoral  vein  of  a  case  of  phlegmasia 
alba  dolens,  twice  natural  size. 

E.—  The  portion  of  the  tissue  shown  in  the  square,  magnified 
20  diameters.  A  large  thrombus  is  attached  to  the  diseased  internal 
coat  of  the  vessel. 

123 


NORMAL  BLOOD.1 

The  examination  of  a  drop  of  blood  spread  upon  a  slide  and 
stained  with  hematoxylon  and  eosin  shows  two  kinds  of  cells: 

1.  Small  circular  masses  colored  in  a  homogeneous  manner 
by  the  eosin  and  entirely  without  a  nucleus — the  red  blood 
corpuscles. 

2.  Other  protoplasmic  masses,  a  little  larger  than  the  red 
blood  corpuscles  and  containing  a  nucleus  staining  blue  with 
the  hematoxylon  and  having  finely  granular  cytoplasm— white 
blood  corpuscles,  or  leukocytes.  , 

(A  third  cellular  component  of  the  blood  is  the  platelets,  but 
to  demonstrate  them  it  is  necessary  to  use  a  special  stain— 
Ehrlich's,  Wright's,  Jenner's  or  Leishmann's  stains.  These, 
therefore,  do  not  show  in  this  slide,  and  do  not  appear  in  the 
drawing.) 

The  Red  Corpuscles. —These  have  the  form  of  small  bicon- 
cave-biconvex disks  whose  shape  can  be  most  easily  recognized 
by  gently  varying  the  focus.  Certain  of  the  corpuscles  are 
badly  fixed  or  have  been  injured  in  the  process  of  spreading 
upon  the  slide,  and  some  of  them  may  show  no  definite  form. 
The  size  of  the  corpuscles  is  very  regular  (diameter,  7  to  8  mm.) 
and  knowledge  of  this  may  be  of  use  in  roughly  estimating  the 
size  of  other  objects  with  which  they  may  be  associated. 

The  White  Corpuscles. —These  at  once  divide  themselves 
into  two  classes  according  to  the  presence  or  absence  of  granules 
in  their  cytoplasm: 

(a)  The    granular   leukocytes   have    multilobulated   nuclei, 
hence  are  often  spoken  of  as  pOlynuclear,  but  are  more  correctly 
called  polymorphonuclear  leukocytes.     Their  cytoplasm  contains 
fine  granules  whose  staining  affinities  are  somewhat  variable 
according  to  the  elements  studied.     Some  have  granules  that 
are  almost  colorless — neutrophiles.     Others  have  granules  that 
are  strongly  stained  with  the  red  of  the  eosin— eosinophiles. 

In  order  to  recognize  a  third  variety  of  the  polynuclears,  the 
basophils,  it  is  necessary  to  employ  a  special  method  of  staining 
with  polychrome  blue.  But  the  basophils  are  exceptional  in 
the  normal  blood,  and  only  become  numerous  in  certain  in- 
flammatory reactions  and  the  leukemias. 

(b)  Non-granular  leukocytes  have  homogeneous  protoplasm 
and  spherical   or   incurved   nuclei   without   the  definite  con- 
strictions of   the  polymorphonuclears.     Some   are  about  the 

1  In  this  country  it  is  not  customary  to  make  examinations  of  blood 
corpuscles  except  in  spreads  stained  by  Wright's  method,  by  which  all  of  the 
elements,  including  the  platelets  are  brought  out.  We  suppose  the  author 
knew  this,  but  introduced  the  hematoxylin  and  eosin  preparation  in  order 
that  the  beginner  might  have  a  marked  comparison  between  the  corpuscles 
as  they  occur  in  the  blood,  and  as  he  may  find  them  in  the  tissues.  (TRANS.) 

124 


size  of  the  red  blood  corpuscles.  The  spherical  nucleus  occupies 
almost  the  entire  cell,  the  cytoplasm  itself  scarcely  appearing, 
being  reduced  to  a  narrow  peripheral  coronet.  These  are  the 
lymphocytes  (small  lymphocytes). 

Others,  eight  or  ten  times  larger,  with  abundant  protoplasm 
and  slightly  indented  nuclei  are  the  middle-sized  or  large 
mononuclears  (large  lymphocytes).  Between  the  two  are 
numerous  transition  forms. 


Red  blood 
corpuscle. 


Fig.  52.— Normal  blood. 

A  drop  of  fresh  blood  is  thinly  spread  upon  a  clean  slide,  dried  and  fixed 
with  alcohol-ether,  and  stained  with  hematoxylon  and  eosin,  and 
examined  under  the  oil-immersion  lens.  Magnified  570  diameters. 


A  single  polymorphonuclear  leukocyte  and  many  red  blood 
corpuscles  are  seen.  The  blood  platelets  are  not  "visible  in  this 
preparation,  requiring  special  stains  to  bring  them  out.  Of  the 
6000  leukocytes  found  in  i  c.mm.  of  blood  the  different  varieties 
occur  normally  in  the  following  proportions: 

Polynuclear  neutrophiles 65  per  cent 

Lymphocytes 15 

Mononuclear  and  transition  forms 20 

Eosinophiles I  or  2 

125 


LEUKOCYTOSIS. 

Polynuclears. 

The  specimen  is  a  spread  drop  of  blood,  dried  and  stained 
with  hematoxylon  and  eosin.  In  it  are  found  the  same  ele- 
ments as  were  seen  in  the  preceding  figure— red  blood  corpuscles, 
polymorphonuclears,  lymphocytes,  large  and  middle-sized 
mononuclears. 

But  that  which  distinguishes  this  preparation  from  the 
preceding  and  gives  it  a  quite  different  appearance  is  the  much 
larger  proportion  of  white  blood  cells.  The  increase  is  so  con- 
siderable as  to  make  it  possible  to  appreciate  the  leukocytes 
without  having  recourse  to  methods  of  enumeration.  As  the 
increase  consists  almost  entirely  of  the  polymorphonuclear 
neutrophilic  cells  it  is  clear  that  we  have  to  do  with  a  poly- 
nucleosis  or  leukocytosis.  Such  a  condition  betrays  a  general 
reaction  of  defense  against  an  acute  inflammatory  process. 

The  discovery  of  leukocytosis  is  often  of  clinical  and  diag- 
nostic importance.  In  the  course  of  an  acute  appendicitis, 
for  example,  it  can  serve  to  reveal  transformation  from  the 
latent  state  to  peri-appendicular  abscess  and  to  indicate  neces- 
sity for  operation. 

If,  instead  of  concerning  the  polymorphonuclear  neutrophiles 
the  increase  in  number  affects  the : 

1.  Eosinophils,  it  is  called   eosinophilia.     This   is   observed 
parasitic  affections  (hydatid  cysts,  intestinal  parasites). 

2.  Mononuclears — if  the  large  or  middle-sized  mononuclears 
are  increased— mononucleosis— it  usually  indicates  the  presence 
of  some  special  form  of  infection  such  as  variola  or  vaccinia. 

Differential  Diagnosis. — By  the  examination  of  stained 
blood  films  one  should  be  able  to  differentiate  between  leukemia 
and  leukocytosis: 

(a)  Through  the  great  number  of  lymphocytes  in  leukemia  of 
the  lymphatic  type. 

(b)  Through  the  presence  of  new  elements  of  the  myeloid 
series  (myelocytes)  in  the  myeloid  variety. 


126 


Red  blood 
corpuscle. 


Poly- 
morpho- 
nuclear. 


Fig.  53.— Leukocytosis. 

A  spread  of  blood  taken  from  a  pneumonic  patient  at  the  period  of  acme. 
Fixation  with  alcohol-ether,  staining  with  hematoxylon  and  eosin. 
Magnified  570  diameters.  There  are  eight  polymorphonuclears  in  the 
field. 

A  count  of  the  blood  corpuscles  made  at  the  same  time  showed 
24.000  leukocytes  of  which  85  per  cent  were  polymorphonuclears. 


127 


MYELOGENIC  LEUKEMIA. 

The  drawing,  like  the  preceding,  shows  a  spread  of  dry 
blood  as  it  appears  under  the  oil-immersion  objective.  The 
enormous  number  of  white  blood  cells  as  compared  with  the 
red  blood  cells,  as  well  as  the  varying  types  of  leukocytes,  give 
the  specimen  a  very  characteristic  appearance  which  should 
at  once  make  one  think  of  leukemia.  This  can  be  confirmed 
by  a  blood  count,  which  will  show  that  the  number  of  the  red 
blood  corpuscles  is  not  increased,  while  that  of  the  white  blood 
corpuscles  is. 

The  leukocytes  are  of  different  types:  (a)  Leukocytes  with 
polylobed  nuclei  and  finely  granular  cytoplasm— polymorpho- 
nuclear  neutrophiles.  (b)  Mononuclears  with  pale  nuclei, 
some  showing  fine  protoplasmic  granulations.  These  are  called 
myelocytes  because  under  normal  conditions  they  are  only 
found  in  the  marrow  of  the  bones,  (c)  Some  lymphocytes  or 
small  mononuclears  with  very  little  protoplasm  and  nuclei 
rich  in  chroma  tin.  (d)  Eosinophils,  more  numerous  than  in 
the  normal  state,  as  they  are  easily  found,  (e)  White  blood 
cells  with  atypical  karyokinetic  figures  in  the  nuclei. 

Finally,  there  are  cells  of  an  entirely  abnormal  type,  the 
normoblasts  or  nucleated  red  blood  corpuscles.  These  are  cells 
not  found  in  the  normal  blood,  belonging  solely  in  the  bone 
marrow  from  which  the  adult  red  blood  cells  are  derived. 

The  morphological  alterations  of  the  red  blood  corpuscles 
should  also  be  pointed  out.  They  consist  of  deformity- 
elongation,  oval  or  rectangular  shape — and  constitute  what  is 
described  as  poikilocytosis.  There  are  also  anomalies  referable 
to  artefacts  in  making  the  preparation,  and  indicate  no 
more  than  fragility  of  the  red  blood  corpuscles.  (Crenation, 
or  chestnut-burr  appearance,  not  shown  in  the  drawings, 
usually  uniformly  affects  all  of  the  red  blood  corpuscles  in  a 
field.) 

Resume.— The  augmentation  in  the  number  of  white  blood 
corpuscles  (which  sometimes  gives  the  fluid  blood  a  truly 
milky  appearance)  beyond  the  limits  occurring  in  infection, 
and  the  preservation  of  the  red  corpuscles,  suggest  the 
diagnosis  of  leukemia.  The  presence  of  the  cells  of  the  bone 
marrow  series — granular  myelocytes  and  normoblasts — permit 
one  to  differentiate  between  the  myelogenic  leukemia  and  lym- 
phatic leukemia  in  which  the  augmentation  in  number  is  in  the 
lymphocytes. 

128 


Normo- 

^      ft^\ 

blasts 

»«>,      A  '     jfc^     ^~^ 

,   (nucleated 
red  blood 
cor- 

ftV-       « 

puscles)  . 

w 

„  Mononu- 

clear. 

ft  * 

A 

Mono- 

*-*Jr     &}&    '  ^y 

"   nuclear. 

^P                   ^-                         '          I   ,  \-llll  >1lr  i- 

cytes. 

Q&             /• 

1 

UB' 

yNw              A^      '      *&P 
^*,            X* 

1    Myelo- 

r.vt.p  ^vit.Vi 

Red  blood 

corpuscle. 

Poly- 

morpho- 

nuclear 

neutro- 

phile. 


Karyo- 
kinesis 
of  leuko- 
cyte. 


Eosino- 
phile. 


Fig.  54. — Blood  of  myelogenic  leukemia. 

Spread  fixed  with  alcohol-ether,  stained  with  hematoxylon  and  eosin,  and 
examined  under  a  magnification  of  570  diameters. 

Note  the  great  number  of  white  as  compared  with  red  cells;  the 
various  types  of  white  corpuscles — polymorphonuclear  neutrophiles, 
eosinophiles,  middle-sized  mononuclears,  lymphocytes,  granular 
myelocytes,  leukocytes  with  karyokinetic  figures,  and  lastly  the 
nucleated  red  corpuscles  or  normoblasts. 


129 


ACUTE  LYMPHATIC  LEUKEMIA. 

As  in  the  preparation  of  myelogenic  leukemia,  one  is  struck 
with  the  enormous  proportion  of  white  relatively  to  the  red 
cells.  Besides  this,  a  preliminary  blood  count  of  both  red  and 
white  cells  shows  that  the  number  of  leukocytes  has  increased 
in  considerable  proportions  (from  20  to  200,000,  according  to 
the  case). 

But  the  white  corpuscles  are  all  lymphocytes,  of  which  there 
are  two  types: 

1.  The  small  lymphocytes,  with  very  little  cytoplasm  forming 
a  narrow  coronet  about  an  ovoid  nucleus. 

2.  The  large  lymphocytes,  or  macrolymphocytes,  which  are 
much  larger  cells  with  larger  and  often  irregular  nuclei  and 
relatively  abundant  protoplasm. 

These  two  different  forms  of  leukocytes  result  from  two 
different  reactions  in  the  lymphatic  tissues.  The  small  lympho- 
cytes express  a  chronic  disturbance — chronic  lymphatic  leukemia. 

The  large  lymphocytes  represent  a  younger  type  of  element, 
less  differentiated  than  that  which  circulates  in  the  blood, 
indicating,  as  in  the  present  case,  an  acute  reaction — acute 
lymphatic  leukemia. 

There  are  intermediates  between  these  extreme  types,  but  in 
this  case  the  large  lymphocytes  being  a  great  deal  more  numer- 
ous than  the  others,  we  have  to  do  with  a  case  of  acute  leukemia. 

In  leukemia  both  the  red  corpuscles  and  the  leukocytes  are 
very  fragile,  so  that  as  the  blood  is  spread  for  staining,  they  are 
easily  deformed  and  crushed. 

In  the  preceding  drawing  there  are  numerous  fragments  of 
cells  that  must  not  be  mistaken  for  blood  platelets,  which,  as 
has  been  said,'  do  not  show  in  smears  stained  with  hematoxylon 
and  eosin,  but  require  special  staining  (Wright's  stain). 

Some  normoblasts  and  plasmocytes  can  also  be  found  in  the 
preparation. 

Resume.— The  formidable  increase  in  the  number  of  white 
blood  corpuscles  and  the  relative  preservation  in  the  number 
of  the  red  corpuscles  is  sufficient  to  suggest  the  diagnosis  of 
leukemia.  The  occurrence  of  lymphoid  cells  (lymphocytes  and 
above  all  large  lymphocytes)  is  sufficient  to  enable  the  diagnosis 
of  acute  lymphatic  leukemia  to  be  made. 


130 


Small  lym- 
phocyte. 


Large  lym- 
phocytes. 


Red  blood 
corpuscle. 


Fig.  55. — Acute  lymphatic  leukemia. 

Fixed  with  alcohol-ether,  stained  with  hematoxylon  and  eosin.     Magnified 
600  diameters. 

The  great  number  of  lymphocytes,  especially  large  lymphocytes 
is  to  be  observed  as  characteristic  of  acute  lymphatic  leukemia. 


131 


NORMAL  KIDNEY. 
Kidney  of  an  Executed  Criminal. 

Diagnosis  of  the  Organ. — The  section  of  the  kidney,  includ- 
ing both  cortex  and  medulla,  appears  to  be  divided  into  two 
distinct  portions.  The  one,  darker,  and  at  the  periphery, 
contains  in  its  interior  a  number  of  small  rounded  masses. 
These  are  the  characteristic  elements  of  kidney  structure,  the 
glomerules,  or  Malpighian  bodies,  which  should  always  be 
looked  for  with  care  in  order  to  make  the  diagnosis  of  the 
organ,  and  to  recognize  its  cortical  substance. 

The  other  paler  portion  consists  of  tiny  tubules,  sometimes 
cut  transversely,  sometimes  longitudinally  and  arranged  in  a 
radiating  fashion:  this  is  the  medulla,  much  less  characteristic 
than  the  cortex  for  making  the  diagnosis  of  the  organ. 

i.  In  the  cortical  substance  the  glomerules,  or  Malpighian 
bodies,  are  of  much  the  same  size  in  the  normal  kidney;  some, 
however,  being  cut  tangentially,  appear  smaller.  The  Mal- 
pighian bodies  consist  of  two  parts:  one  central,  the  vascular 
tuft;  the  other,  peripheral,  the  capsule  of  Bowman. 

The  vascular  tuft  is  a  sort  of  undifferentiated  plasmodium, 
that  is  to  say,  a  protoplasmic  mass  not  divided  into  cells,  in 
the  substance  of  which  one  perceives  a  great  number  of  nuclei 
and  numerous  capillaries  containing  red  blood  corpuscles. 
About  it  there  is  a  narrow  space  limited  on  the  outside  by  the 
capsule  of  Bowman. 

It  has  a  delicate  endothelial  (epithelial?)  lining.  Here  and 
there  in  the  section  it  may  be  possible  to  find  glomeruli  that 
show  the  vascular  pole,  formed  of  two  vessels,  the  afferent  artery 
and  efferent  vein,  or  the  urinary  pole,  at  which  the  uriniferous 
tubule  begins. 

The  glomerules  are  surrounded  by  a  large  number  of  tubules 
of  unequal  diameter  sometimes  cut  transversely,  sometimes 
longitudinally. 

Examination  under  the  low  power  enables  one  to  recognize 
two  principal  types:  Secretory  tubes  (convoluted  and  irregu- 
lar tubes)  and  excretory  tubes,  ascending  and  descending  loops 
of  Henle. 

(a)  The  secretory  tubes:  These,  known  as  the  convoluted  tubules, 
are  recognized  by  a  lining  of  granular  epithelium,  more  or  less 
acidophilic  and  peculiarly  fragile.  It  is  very  common  for  kidney 
tissue  taken  from  autopsy  cases  to  show  cadaveric  alterations 
in  a  variety  of  forms  such  as  desquamation  and  protoplasmic 

132 


Malpig- 
hian 

bodies  or 

glomer- 

ules. 

Convo-  f 
luted  or  I 
secretory] 
tubules. 


Arteriole. 


Venule. 

Tubules 

of  Henle 

or  excretory 

tubules  cut 

parallel. 

Excretory 
tubules 
cut  trans- 
versely. 


Cortical 
substance. 


Medullary 
substance. 


Fig.  56. — Normal  kidney. 


Stained  with  hematoxylon  and  eosin.     Magnified  40  diameters. 

The  greater  part  of  the  drawing  shows  the  renal  cortex  in  which  a 
great  many  Malpighian  bodies  or  glomerules  can  be  seen  among 
the  convoluted  tubules.  The  capsule  has  been  torn  of  and  does  not 
appear  in  the  section.  The  lower  right-hand  corner  shows  the 
medullary  substance  with  its  excretory  tubules  cut  transversely 


133 


fragmentation;  one  must  be  careful  not  to  mistake  them  for  path- 
ological lesions.  They  can  usually  be  recognized  through  uniform 
occurrence  in  all  parts  of  the  section.  Such  cadaveric  changes 
begin  to  make  their  -appearance  a  few  hours  after  death. 

The  cells  of  the  secretory  tubules  are  mostly  cubical,  possess 
a  nucleus  situated  basally  and  show  in  well-fixed  specimens, 
even  with  the  ordinary  stains,  a  fine  fringe  upon  the  centrally 
directed  surface— the  so-called  rodded  epithelium. 

(b)  The  excretory  tubules:  These  are  of  two  varieties.  The 
first  differ  from  the  convoluted  tubules  by  an  epithelium  with 
more  distinctly  basophilic  staining  reactions,  in  a  much  better 
state  of  preservation,  as  they  are  much  less  fragile.  The  cells 
have  a  bluish  cast  and  darker  nuclei  than  those  of  the  secretory 
tubules.  They  comprise  the  larger  or  ascending  limbs  of  Henle's 
loop.  The  others  are  fine  tubules  lined  with  an  extremely 
flattened  epithelium  resembling  endothelium,  and  have  a 
general  appearance  not  unlike  capillaries,  but  are  easily  differ- 
entiated from  them  through  the  complete  absence  of  red  blood 
corpuscles  from  their  interiors.  They  correspond  to  the  descend- 
ing limb  of  Henle's  loop  or  to  the  loop  itself. 

2.  In  the  medullary  substance  are  found  nothing  but   the 
transverse  and  longitudinal  sections  of  tubules  of  various  kinds 
— excretory  tubules,  ascending  and  descending  limbs  of  Henle's 
loops  just  studied  in  the  cortical  portion,  and  much  larger 
collecting  tubes  lined  with  tall  cubical  epithelium — the  collect- 
ing tubes  of  Bellini. 

3.  Besides   these   epithelial   components   one   sees   the   fine 
vascular  and  connective  tissue  of  the  organ.     The  connective 
tissue  consists  sometimes  of  a  young  tissue  rich  in  cells — more 
frequently  of  collagenous  fibers.     The  vessels,  always  large  and 
abundant,  are  of  the  adult  type. 

Such  is  the  picture  presented  by  a  histological  section  of  the 
normal  kidney,  and  such  are  the  landmarks  that  one  must 
know  to  recognize  the  parenchyma  with  which  one  chiefly  has  to 
do  in  recognizing  the  pathological  alterations. 

With  regard  to  the  renal  lobule,  represented  by  the  unity  of 
the  uriniferous  tubule,  it  is  impossible  to  gain  information 
through  study  of  the  different  parts  of  a  section.  It  is  a  con- 
ception acquired  through  the  study  of  tissues  specially  prepared 
by  injection  methods. 

In  the  pathological-histological  study  of  the  kidney,  that 
which  is  of  most  importance  is  the  recognition  of  the  excretory 
and  the  secretory  structures. 

134 


Endothe- 
lium. 

Glomer- 
ule. 


Capsule  of 
Bowman. 


W^ 

>e  *       *»*-,  —  - 

W^ 

y£fe^vV:> 

•TuatrfcS  •'•  •;•-;  •    -  , 

r^^.^V^- 
^*;* ••;*.  •*  •  '••**$•* 

,,,;.«     9  :-••   ..    •_    ••••_  . 


Afferent 
artery. 

Convo- 
luted 
tubule. 


B 


Descend- 
ing limb 
of  Henle's 
loop. 


Capillary 

containing 

blood. 


Ascending 
limb  of 
Henle's 
loop. 

Duct  or 
tubule  of 
Bellini. 


Capillary. 


Fig.  57. — Normal  kidney. 
Stained  with  hematoxylon  and  eosin.     Magnified  250  diameters. 

Above  A,  the  cortical  substance  is  shown.  In  it  are  a  Mal- 
pighian  body,  convoluted  tubules  and  some  excretory  tubules. 

Below  B,  the  medullary  substance  is  shown  with  its  -various  excre- 
tory tubules  cut  transversely. 


135 


SUBACUTE  NEPHRITIS. 

Variolous  Nephritis. 

Diagnosis  of  the  Organ.— Upon  examining  the  section  with  a 
low-power  lens  it  is  easy  to  recognize  the  Malpighian  bodies 
whose  capillary  tufts  are  characteristic  and  at  once  enable  the 
organ  to  be  diagnosed. 

Diagnosis  of  the  Lesion.  —The  lesions  presented  in  the  section 
are  very  varied.  To  understand  them  it  will  be  necessary  to 
study  in  detail  the  glandular  parenchyma  (glomerules  and 
convoluted  tubule)  and  the  stroma  or  interstitial  tissue. 

At  the  upper  part  of  the  section,  shown  in  the  drawing  (Fig. 
58),  there  is  a  thick  layer  of  connective  tissue  containing  some 
fat  cells.  It  is  the  capsule  of  the  organ  which,  in  this  case,  is 
abnormally  thick  and  contains  a  few  small  lymphocytic  col- 
lections (inflammatory  cells).  This  thickening  of  the  capsule 
with  inflammatory  infiltration  denotes  a  long-standing  inflam- 
matory process. 

Below  the  capsule  the  cortical  substance  shows  extremely 
complex  alterations  affecting  both  the  glomerules  and  tubules 
(glomerulo-nephritis) . 

(a)  The  glomerules  have  a  very  variable  size  and  structure. 
The  next  drawing  (Fig.  59)  shows  two  different  portions  from 
the  section,  taken  at  random,  and  shown  under  a  higher  mag- 
nification.   One  (A)  shows  a  glomerule  whose  capsule  of  Bow- 
man is  greatly  thickened  through  stratified  layers  of  connective 
tissue  composed  of  collagen  fibers,  among  which  are  numerous 
long  bluish  nuclei.     In  the  center  of  the  capsule  the  vascular 
elements   of    the   glomerulus    show   with    some   exaggeration 
because  of  the  large  number  of  red  blood  corpuscles  they  contain, 
and  by  which  the  nuclei  of  the  plasmodium  are  obscured  (con- 
gestion).    On  the  left-hand  side  of  Fig.  59,  A,  there  is  a  glom- 
erular  lesion  of  an  entirely  different  kind.     The  sclerosis  of  the 
capsule  has  invaded  the  entire  glomerule  and  the  capillary 
structure  can  no  longer  be  seen.     The  vascular  strophy  and 
the  thickening  of  the  capsule  of  Bowman  have  terminated  in 
a  glomerulo-capsular  symphysis,  and  the  formation  of  a  rounded 
mass  of  fibrous  substance  to  which  the  term  "wafer"  is  some- 
times applied.     This  is  another  indication  that  the  lesion  is 
old.     Throughout  the  section  there  are  all  stages  between  the 
two  types  of  lesion  described. 

(b)  In  the  intervals  between  the  glomerules  the  secretory 

136 


Capsule. 


Inflamma- 
tory in- 
filtration. 


Cystically 
dilated 
tubules 
containing 
inter- 
casts. 


Fig.  58. — Subacute  nephritis. 


Fibroid 
glomerule. 

Vessel 
with  peri- 
pheral 
sclerosis. 

Inflammed 
stroma. 

Glomer- 
ules  in 
different 
stages  of 
sclerosis. 


Inflam- 
matory 
infiltra- 
tion. 


Stained  with  hematoxylon  and  eosin.     Magnified  40  diameters. 

Below  the  thickened  capsule  shown  at  the  top  of  the  drawing, 
the  kidney  substance  shows  a  variety  of  glomerular  and  tubular 
lesions  (glomerulo-nephritis} .  Between  the  glomerules  and  the 
tubules  there  is  considerable  infiltration  of  inflammatory  cells. 


137 


tubes  show  lesions  more  or  less  important.  In  Fig.  59,  B,  on 
the  next  page,  the  cylindrico-cubical  epithelium  is  disposed 
around  an  opening  sometimes  potential,  sometimes  com- 
pletely disappeared.  The  lumen  is  found  stuffed  with  des- 
quamated cells  with  pycnotic  nuclei  crowded  pell-mell  into 
the  center  of  a  cavity  more  or  less  sinuous.  Here  and  there, 
as  in  the  right  side  of  the  Fig.  59,  B,  the  desquamation  of  the 
epithelium  is  less  marked,  but  the  tubes  tend  to  dilatation 
and  cystic  transformation.  The  lumen  becomes  a  kind  of 
cavity  that  is  filled  with  hyaline  fluid  that  stains  distinctly 
with  the  eosin  dye  and  is  lined  by  flattened  epithelium. 

These  lesions  of  the  tubule  comprise  desquamative  and  exuda- 
tive tubulitis  and  are  certainly  not  postmortem  alterations  or 
artefacts  due  to  bad  fixation  of  the  tissue.  Such  cystic  appear- 
ances are  never  found  under  such  circumstances. 

(c)  Besides  the  lesions  of  the  parenchyma  there  are  less 
marked  alterations  of  the  stroma  characterized  by  an  enor- 
mous infiltration  of  small  round  cells  (bluish)  placed  imme- 
diately beneath  the  capsule  (Fig.  58).  These  cells  infiltrate 
more  or  less  everywhere  between  the  glomerules  and  about  the 
tubules,  accumulating  here  and  there  in  masses  more  or  less 
distinct  and  clear  cut. 

Finally  are  to  be  noted  small  interstitial  hemorrhages,  easily 
recognized  by  their  brownish  color  with  occasional  traces  of 
pigmentary  change. 

In  addition  to  all  this,  the  walls  of  the  bloodvessels  are 
thickened  through  stratifications  of  young  connective  tissue. 

The  medullary  substances,  not  shown  in  the  drawing,  is  not 
distinctly  affected.  In  the  excretory  tubules,  however,  collec- 
tions of  desquamated  cells  indicate  lesions  further  up  the  tubules. 
In  some  of  these  cells  the  details  of  nuclear  structure  can  still 
be  seen;  others  have  undergone  hyaline  change. 

Resume.— Nephritis  of  the  subacute  variety,  affecting  at 
the  same  time  the  glomerules  and  the  tubules  (glomerulo- 
nephritis  in  different  stages)  and  the  stroma.  In  consequence 
it  is  a  mixed  nephritis,  as  is  usually  the  case  if  of  sufficient 
duration  to  effect  changes  of  the  interstitial  tissue  which  always 
requires  more  time  than  the  injury  to  the  epithelium.  Hence 
the  old  division  into  interstitial  and  paranchymatous  nephritis 
is  too  artificial  to  be  valid. 

This  type  of  subacute  nephritis  is  common  after  scarlatina 
and  variola. 

138 


Glomerule 
with  con- 
gested 
capillary 
tuft,  and 
thickened 
capsule. 


Connec- 
tive tissue 
F/t   stroma. 


Diseased 
secretory 
tubule. 

Normal 

excretory 

tubules. 

Convo- 
luted 

tubules  in 
a  state  of 
cystic  dila- 
tation, 
and  con- 
taining 
tube- 
casts. 


Secretory 
tubules. 


Fig.  59.— Subacute  nephritis. 
Stained  with  hematoxylon  and  eosin.     Magnified  250  diameters. 

Nephritis  from  a  case  of  smallpox. 

A.— Two  inflammed  glomerules  in  different  stages  of  disease. 
B.— Diseased  convoluted  tubules  with  desquamated  epithelium, 
cystic  dilatation  and  tube  casts. 

139 


CHRONIC  NEPHRITIS. 

Bright's  Disease. 

Diagnosis  of  the  Organ.— The  diagnosis  of  the  organ  is 
easily  made,  thanks  to  the  characteristic  aspect  of  the  glomerules. 

Diagnosis  of  the  Lesion. — As  in  the  preceding  case  it  is 
necessary  to  study  the  changes  in  both  epithelial  and  con- 
nective tissue  elements. 

A.  The  Malpighian  bodies,  or  glomerules,  present  alterations 
much  like  those  of  the  subacute  form  of  the  disease,  but  more 
distinct.     The  progressive  transformation  of  the  glomeruli  into 
fibrous  masses  (wafers)  is  marked.     At  first  the  capillary  tuft 
retracts  toward  one  pole,  only  occupying  a  part  of  the  capsular 
cavity,  then  it  unites  itself  with  the  capsule  of  Bowman  and 
finally  degenerates  altogether  and  becomes  a  mass  of  collagenous 
material. 

B.  The  convoluted  tubules  do  not  show  any  disturbance  that 
can  be  attributed  to  cadaveric  change,  but  under  the  capsule  of 
the  kidney  they  undergo  a  dilatation  that  is  quite  marked  and 
explains  the  little  bosselations  that  appear  upon  the  surface 
of  the  kidneys  of  cases  of  Bright's  disease,  and  remain  as  small 
pale  spots  when  the  capsule  of  the  organ  is  torn  off.     The 
drawing  shows  two  of  these  granulations  separated  by  a  slight 
groove,  at  the  bottom  of  which  an  infiltration  of  blue  cells 
(lymphocytes)   can  be  seen.     The  ectasia  of  the  convoluted 
tubules  in  the  neighborhood  of  these  granulations  is  referable 
to  functional  activity  of  the  organ  (compensatory  hypertrophy). 

C.  The  stroma  also  shows  important  changes.     The  masses 
of  bluish  cells  between  the  glomerules  and  the  tubules  some- 
times indicate  an  inflammatory  reaction  of  chronic  nature, 
sometimes   a   terminal   process — an   addition   of   a   subacute 
nephritis  to  a  chronic  sclerotic  one. 

The  vessels  have  extremely  thick  walls;  their  lumen  is  corre- 
spondingly diminished,  and  almost  obstructed  by  the  enormous 
proliferation  of  the  middle  and  internal  coats. 

In  the  medullary  substance,  not  shown  in  the  drawing,  the 
lumina  of  the  collecting  tubes  is  obstructed  by  rounded  masses 
of  homogeneous  substance — tube  casts. 

Resume.  — Nephritis,  whose  lesions  affect  chiefly  the  glom- 
erules and  stroma,  and  relatively  spare  the  convoluted  tubules. 
The  stroma  and  parenchyma  are  both  affected,  again  showing 
the  artificial  character  of  the  old  division  into  interstitial  and 
parenchymatous  nephritis. 

140 


Dilated 
tubules 
forming  a 
"granu- 
lation of 
Bright." 

Fibroid 

glomer- 

ules. 


Excretory 
tubule. 


f  "Granu- 
\  lation  of 
I  Bright" 


Malpig- 
hian  body 

Inflam- 
matory 
infiltra- 
tion. 


Thickened 
capsule  of 
Bowmann. 


Arteriole 

with 

thickened 

walls. 


Fig.  60.— Chronic  nephritis. 
Stained  with  hematoxylon  and  eosin.     Magnified  45  diameters. 

Section  of  a  small  sclerotic  kidney  of  Bright' s  disease.  At  the 
upper  edge  two  of  the  so-called  granulations  of  Bright  project 
upon  the  surface  beneath  the  capsule.  The  glomerular  and  peri- 
vascular  sclerosis  is  striking. 

141 


PYEMIC  NEPHRITIS. 
Embolic  Nephritis. 

Diagnosis  of  the  Organ. — This  is  relatively  difficult  because 
of  the  extent  of  the  lesions.  At  certain  points,  however,  as  in 
the  lower  part  of  the  drawing,  it  is  possible  to  discover  some 
glomerules  and  convoluted  tubules. 

Diagnosis  of  the  Lesion. — Under  a  low-power  lens  one  is  at 
once  struck  by  the  pale  color  of  the  renal  elements.  The 
cellular  limits  are  indistinct,  both  those  of  the  tubules  and 
the  glomerules.  The  nuclei  have  often  disappeared  from  the 
cells.  The  tubules  are  often  filled  with  amorphous  eosinophilic 
masses.  This  necrotic  aspect  of  the  parenchyma  is  in  accord 
with  the  vascular  alterations.  The  preparation  is  mottled 
with  dark  bluish  patches  which  are  even  visible  to  the  naked  eye. 

These  are  abscesses  and  can  be  seen  in  the  upper  part  of 
the  drawing.  With  a  higher  magnification  they  are  seen  to 
be  made  up  of  acidophilic  cells  with  oval  or  multilobed  nuclei 
(mononuclear  and  polymorphonuclear  leukocytes).  The  acido- 
philic quality  of  the  protoplasm  and  the  pycnosis  of  the  nuclei 
indicate  a  marked  cellular  degeneration — pus.  At  the  periph- 
eral limit  of  the  abscess  the  necrosis  is  particularly  marked 
by  a  zone  of  hyaline  amorphous  substance  in  which  one  can 
recognize  tubules  and  glomerules.  The  abscesses  are  formed  by 
a  diffuse  infiltration  of  inflammatory  cells,  mononuclear  and 
polymorphonuclear  cells,  some  of  which  lie  between  the  tubules 
and  some  in  the  thickness  of  their  walls. 

In  addition  to  these  microscopic  abscesses  there  are  much 
smaller  dark  spots  extremely  irregular  in  form  having  a  finely 
granular  appearance  and  distributed  without  any  order  through- 
out the  specimen.  These  are  masses  of  bacteria  mostly  com- 
posed of  great  numbers  of  cocci  that  can  be  rendered  more 
distinctly  visible  by  special  methods  of  staining,  especially 
Gram's  stain.  They  are  microbic  emboli  brought  by  the 
blood  from  sources  outside  of  the  kidney.  In  the  center  of 
the  drawing  is  a  glomerule  containing  such  a  microbic  embolus. 

Thus  is  explained  the  origin  of  the  abscesses.  •  The  paren- 
chymatous  necrosis  is  due  to  the  presence  of  the  areas  of  sup- 
puration and  to  the  vascular  thrombosis. 

Resume.— Pyemic  nephritis,  with  numerous  abscesses  and 
microbic  emboli,  such  as  occur  in  septicemia,  and  result  from 
embolism. 

142 


Microor- 
ganismal 
embolus. 


Necrotic 
tubules 
with 

interstitia 
inflam- 
matory 
infiltra- 
tion. 


Malpig- 
hian 
ody. 

Convo- 

ited 
tubules. 


Embolic  and  foci  of  suppuration. 


Fig.  61. — Pyemic  nephritis. 
Stained  with  hematoxylon  and  eosin. 

Embolic  nephritis  in  a  boy,  aged  fourteen  years,  dying  from 
septico-pyemia  following  acute  osteomyelitis  of  the  tibia. 

A. —  The  fragment  of  the  kidney  as  it  appears  when  twice  mag- 
nified. 

B. — Numerous  abscesses  and  microorganismal  emboli  are  seen 
in  the  upper  part  of  the  drawing,  with  necrotic  renal  tissue  below. 
Magnification  30  diameters. 

143 


ASCENDING    PYELONEPHRITIS. 

Urinary  Nephritis. 

Diagnosis  of  the  Organs. —Under  the  low  power  it  is  easy  to 
recognize  the  Malpighian  bodies,  the  convoluted  tubules  and 
the  collecting  tubes  of  the  kidney. 

Diagnosis  of  the  Lesion.— One  is  at  once  struck  by  the 
dissociation  of  the  histological  elements  and  by  the  diminution 
of  the  staining  affinity  of  the  cellular  elements. 

A.— In  the  cortex  (Fig.  62,  C)  the  convoluted  tubules  present 
alterations  analogous  with  those  described  in  connection  with 
the  subacute  nephritis.  In  the  interior  of  more  or  less  irregular 
cavities  desquamated  epithelial  cells  are  mixed  with  many 
smaller  cells :  mononuclears  and  more  rarely  polymorphonuclear 
cells. 

The  glomerules  are  less  numerous,  being  crowded  out  by  the 
inflammatory  infiltration  which  dissociates  all  of  the  structures. 
Those  that  persist  show  varying  congestion  and  capsular  pro- 
liferation. An  enormous  number  of  blue  cells  diffusely  infil- 
trate the  entire  stroma;  in  addition  to  which  there  are  numer- 
ous dilated  capillaries  and  small  discrete  interstitial  hemorrhages. 

B.— In  the  medulla  (Fig  62,  B)  the  parallel  excretory  tubules 
with  their  lining  of  cubical  cells  are  relatively  intact.  Inside 
of  them  are  two  kinds  of  elements:  pus  cells,  i.  e.,  polymorpho- 
nuclear and  mononuclear  leukocytes  more  or  less  degenerated 
with  acidophilic  protoplasm  and  pycnotic  nuclei;  and  desqua- 
mated epithelial  cells.  The  radiating  appearance  of  the  collect- 
ing tubules  filled  with  pus  and  degenerated  epithelium  is  char- 
acteristic of  a  nephritis  of  ascending  origin  (radiating  nephritis 
of  cystitis,  prostatitis  and  urinary  obstruction).  In  the  inter- 
spaces between  the  tubules  the  stroma  assumes  a  hyaline 
aspect:  fine  connective- tissue  fibrillae  infiltrated  with  edema- 
tous  fluid,  and  here  and  there,  with  numerous  inflammatory 
cells  sometimes  difficult  to  distinguish  from  the  nuclei  of  the 
fixed  connective-tissue  cells.  In  the  medulla,  as  in  the  cortex, 
there  are  numerous  capillary  vessels,  dilated  and  sometimes 
ruptured  (interstitial  hemorrhages). 

Resume.— A  scending  radiating  nephritis  with  parenchyma- 
tous  changes  (desquamation  of  the  cells)  as  well  as  important 
interstitial  changes. 


144 


Medullary  substance. 


Cortical  substance 


Abnormal 

excretory 

tubules. 


Vessel. 


Secretory 

tubules 

containing 

poly- 

morpho- 

nuclear 

cells. 


Dilated 
capillary. 


Excretory 
tubule. 


Fig.  62. — Ascending  pyelonephritis. 

Stained  with  hematoxylon  and  eosin. 

Pyelonephritis  following  a  gunshot  wound  of  the  dorsal  spinal 
cord  with  paraplegia  and  retention  of  urine.  The  infection 
following  the  repeated  catheterizations  was  the  cause  of  death. 

A.— Appearance  of  a  fragment  of  the  kidney  magnified  5  diam- 
eters. 

B. — Medullary  substance.     Magnified  100  diameters. 

C. — Cortical  substance.    Magnified  100  diameters. 
10  145 


TUBERCULOUS  PYELONEPHRITIS. 
Tuberculosis  of  the  Kidney. 

The  section  has  been  made  in  the  neighborhood  of  a  tuber- 
culous cavity  or  excavation.  It  is  divisible  into  three  zones; 
an  upper  which  is  the  edge  of  the  excavation,  a  middle  in  which 
the  kidney  tissue  is  relatively  undisturbed,  and  a  lower. 

Diagnosis  of  the  Organs.  —This  can  easily  be  made  by  noting 
the  presence  in  the  middle  zone  of  Malpighian  bodies  and 
convoluted  tubules. 

Diagnosis  of  the  Lesion.— To  accomplish  this  it  will  be 
necessary  to  separately  examine  the  upper  and  lower  thirds. 

I.  Upper  Third.— This  is  the  wall  of  the  tuberculous  excava- 
tion.   It  is  composed  of  a  caseous  mass  of  a  blue-violet  color 
that  is  quite  characteristic  and  has  an  undifferentiated  appear- 
ance in  which  remnants  of  nuclei  can  be  seen.     It  also  shows 
numerous  fractures  or  cracks  that  are  caused  by  retraction 
effected  by  the  reagents  used  in  the  preparation  of  the  specimen 
for  histolqgical  examination.    At  the  periphery  of  the  caseous 
mass  some  epithelioid  cells  are  seen  with  stretched-out  nuclei 
and  pale  and  abundant  protoplasm,  and,  above  all,  lymphocytes 
forming  a  dense  bluish  layer  at  the  extreme  edge  of  the  wall  of 
the  excavation,  and  extending  into  the  parenchyma. 

II.  Middle  Third.— This  shows  the  parenchyma  variously 
disturbed  by  disease.     Above,  near  the  edge  of  the  excavation, 
the  tubules  are  deformed  and  compressed:    lower  down  they 
are  normal  in  appearance.     In  the  secretory  tubules  desquama- 
tion  of  the  epithelium  is  quite  pronounced  (tubulitis).     The 
glomerules  are  but  little  altered  (congestion)  but  the  stroma 
presents  an  important  lymphocytic  infiltration  with  edema.     In 
the  lumen  of  some  of  the  excretory  tubules  there  are  reddish 
hyaline  masses  (tube  casts).     The  diminished  staining  power 
of  all  of  the  elements  is  to  be  noted. 

III.  Lower  Third.— This   contains   miliary   tubercles  which 
can  be  recognized  by  their  rounded  form,  by  the  presence  of 
giant  cells  with  nuclei  arranged  in  horseshoe  form,  by  their 
caseous  centers  and  by  the  epithelioid  and  lymphoid  cells  at 
their  peripheries. 

It  is  easy  to  understand  that  with  the  occurrence  of  added 
caseation  evacuation  into  a  calyx  might  occur  and  thus  begin 
a  new  open  excavation. 

Resume.— Pyelonephritis,  not  unlike  the  preceding  case  in 
the  epithelial  desquamation,  the  infiltration  of  the  stroma  and 
the  marked  cellular  necrosis  but  differing  from  it  in  the  presence 
of  the  miliary  tubercles  and  the  excavation. 

146 


Caseous 
matter. 


Epithe- 
lioid 
cells. 


Sclerosed 
glomerule. 

Com- 
pressed 
convo- 
luted 
tubules. 


Convo- 
luted 
tubules. 


L^mphoid 
cells. 


Malpig- 

hian 

glomerule. 


Stroma. 


Miliary 
tubercle. 


Giant 
cells. 


Fig.  63. — Tuberculous  pyelonephritis. 
Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

The  upper  third  of  the  section  shows  a  part  of  the  wall  of  a 
tuberculous  cavity  of  which  the  liquefied  center  cannot  be  seen.  The 
middle  part  is  composed  of  diseased  renal  tissue.  The  lower  part 
contains  a  miliary  tubercle  with  two  giant  cells. 


147 


AMYLOID  INFILTRATION  OF  THE  KIDNEY. 
From  a  Case  of  Chronic  Pulmonary  Tuberculosis. 

Diagnosis  of  the  Organ.— This  is  very  easy  to  make  by  a 
more  extended  study  c^  the*  section  than  the  limited  field  shown 
in  the  drawing  permits.  Xlnder  a  low  power  the  structure  of 
the  organ  is  found  to  be  tubular,  divisible  into  a  cortical 
portion  in  which  the  tubules  twist  and  turn  among  them- 
selves, and  a  medullary  part  in  which  they  occur  in  parallel 
formations— pyramids.  Regularly  distributed  in  the  portions 
of  the  cortex  lying  between  narrow,  fairly  equidistant,  radiat- 
ing, parallel,  linear  formations  composed  of  excretory  tubules 
and  vessels— the  medullary  rays  or  pyramids  of  Ferrein— are 
rounded  structures,  which  though  so  changed  by  disease  that 
they  no  longer  have  the  strawberry  appearance,  are  recogniz- 
able of  the  glomerular  or  Malpighian  bodies.  We  thus  arrive 
at  the  diagnosis  of  kidney. 

Diagnosis  of  the  Lesion.— The  examination  just  completed 
has  shown  the  absence  of  gross  abnormalities;  so  for  future 
study  the  higher-power  lenses  must  be  used.  With  such  mag- 
nification, changes,  such  as  are  represented  in  the  drawing, 
are  readily  found.  They  embrace  abnormalities  of  both 
glomerules  and  tubules. 

1.  The  Glomerular  Disturbance.— A  diseased  glomerule  occu- 
pies the  greater  part  of  the  center  of  the  drawing.     Instead  of 
appearing  as  a  nucleated  plasmodium,  as  is  normal,  it  is  found 
to, '.be  largely  composed   of  structureless,  pink-colored,  waxy 
substance  in  which  a  few  cells  and  nuclei  are  caught,  and 
between  the  masses  of  which  some  of  the  original  structure 
survives.    This  is  amyloid  substance  as  can  easily  be  determined 
by  the  application  of  the  microchemic  tests  already  described. 
Attention  to  the  general  arrangement  of  the  amyloid  material 
shows  it  to  be  deposited  in  a  distribution  corresponding  to  the 
letter  S.     This  suggests  that  its  seat  of  primary  infiltration  has 
been  about  the  little  vessels  of  the  glomerules.     This  is  in 
complete  correspondence  with  its  usual  method  of  infiltration. 
Beginning  its  appearance  about  the  small  vessels,  it  gradually 
infiltrates   the  surrounding   tissue,   crowding  its  proper   cells 
and  causing  them  to  atrophy. 

2.  The   Tubular    Disturbance. — These   occur   in   association 
with  the  amyloid  disease  but  are  in  no  sense  a  part  of  it. 
Though  it  is  rare  for  a  kidney  affected  with  amyloid  disease  to 
be  otherwise  normal,  it  may  be  possible.     The  amyloid  infiltra- 

148 


tion  is  the  result  of  certain  chronic  nutritive,  or  toxic,  disturb- 
ance which  may  result  in  numerous  and  diversified  associated 
changes.  It  is  common,  for  example,  to  find  fibrosis  associated 
with  amyloid.  In  this  particular  case  the  toxic  disturbance  of 
the  patient's  blood  has  manifested  itself  in  tubular  changes 
which  assume  various  appearances  that  may  be  looked  upon 
as  indicating  differing  degrees  of  cell  destruction.  At  the 
lower  right-hand  portion  of  the  drawing  are  two  transverse 
sections  of  convoluted  uriniferous  tubules  (secretory  tubules) 
that  are  fairly  normal  in  appearance.  In  the  upper  left-hand 
portion  there  is  a  section  of  a  similar  tubule  whose  epithelial 
lining  is  transformed  into  an  nuclear  granular  mass— com- 
plete distruction,  or  necrosis  of  the  epithelium.  Below  it  is  a 
section  of  a  slightly  dilated  tubule  whose  cells  contain  an 
excessive  number  of  granules  (cloudy  swelling)  among  which 
are  some  very  large  granules  and  small  spheres  of  translucent 
homogeneous  substance  much  like  the  amyloid,  but  failing  to 
give  the  microchemic  reaction  with  iodine  and  gentian  violet. 
These  are  hyaline.  In  some  of  the  other  tubules  cells  may  be 
observed  to  lie  free  in  the  lumina  of  the  tubules  (desquamation). 
These  cellular  and  tubular  changes  are  not  the  result  of  post- 
mortem autolysis  for  they  lack  uniformity.  They  are  the 
results  of  disease — tubular  nephritis. 

Resume.— Kidney  whose  glomerules  show  homogeneous, 
waxy,  perivascular  deposits  (amyloid),  and  whose  tubules  show 
destruction  and  desquamation  of  the  epithelium  in  varying  in- 
tensity— tubular  nephritis. 


Urinifer- 

ous  tubule 
com- 

21      ;    ^ 

pletely  de- 
generated. 
Vp<«pl 

j 

Granules 

"',£•"              V'V;~v/rO'" 

».  j        ^  O           k                                                             ^^       *       tt.» 

in  cells  of 
a  tubule. 

"';    .     '<- 

•  s.  •«,-   @,  ..            •                         -; 

'4£&*$tH>  .V^ 

'                                   .^Bt^^i^VBJ  Js^fc  V  ' 

substance. 

Vessel. 
Convo- 

tubule. 

Fig.  64. — Amyloid  infiltration  of  a  renal  glomerula.  From  a  patient 
dead  of  chronic  pulmonary  tuberculosis.  Magnified  250  diameters. 
Stained  with  hematoxylin  and  eosin. 

149 


BENIGN  HYPERNEPHROMA. 

Diagnosis  of  the  Organ.  —The  section  shown  in  the  drawing 
divides  itself  into  two  distinct  portions,  which  have  different 
staining  affinities.  In  the  lower,  Mapighian  bodies  and  tubules 
leave  no  doubt  as  to  the  organ  concerned.  This  portion  is 
separated  from  that  above  by  a  thick  band  of  vascular  con- 
nective tissue  which  is  the  capsule  of  the  kidney. 

Diagnosis  of  the  Lesion.— This  constitutes  the  upper  part 
of  the  drawing  and  is  a  tumor.  When  looked  at  closely  it 
consists  of  nests  of  pale  cells  separated  from  one  another  by 
strands  of  connective  tissue  or  by  capillaries. 

The  arrangement  is  irregular  and  the  absence  of  parallel 
columns  is  particularly  noticeable.  The  cells  when  examined 
under  a  higher  power  are  found  to  have  a  transparent  proto- 
plasm, and  slightly  excentric  nucleus  and  a  slightly  reticulated 
or  vacuolated  protoplasm  recalling  that  of  the  spongiocytes  of 
the  zona  fascicularis  of  the  adrenal  body.  Like  them  these 
cells  are  crowded  with  fine  fatty  granules  (lipoid,  neutral  fats). 

Between  the  cell  nests  is  a  fine  trellis  work  of  collagen  fibers. 
Newly  formed  capillaries  are  extremely  numerous  and  are  in 
intimate  contact  with  the  cells  of  the  tumor,  as  in  the  adrenal. 
The  structure  of  these  capillaries  is  normal:  the  endothelium 
reposes  upon  a  thin  layer  of  connective  tissue.  In  the  part 
of  the  drawing  representing  the  kidney,  attention  must  again  be 
called  to  the  fibrous  capsule,  which  separates  it  from  the  tumor, 
and  the  compression  of  the  tubules  in  its  immediate  vicinity. 

We  have  here  to  do  with  a  well-circumscribed  definitely 
limited  tumor  of  glandular  origin,  that  is  to  say,  with  an 
adenoma — a  benign  tumor.  But  the  appearance  of  the  cells 
recalls  the  spongiocytes  of  the  adrenal,  and  on  this  account 
it  has  been  supposed  that  the  tumor  arises  from  debris  of  an 
embryonal  vestige  of  that  organ  included  in  the  kidney  sub- 
stance, from  which  it  derives  the  name  hypernephroma. 

Resume. — It  is  an  epithelial  tumor  starting  from  the  tubules 
of  the  kidney  and  in  which  the  cells,  in  part  or  altogether, 
take  the  pale  appearance.  It  is  possible  sometimes  to  follow 
the  transition  of  the  kidney  cells  to  the  transparent  cells. 

Sometimes  in  this  case  we  have  to  do  with  a  benign  tumor, 
localized  and  encapsulated  and  not  giving  metastasis:  adenoma 
with  pale  cells— benign  hypernephroma. 

Sometimes,  one  finds  the  characteristics  of  malignant  tumors 
of  the  kidney — some  with  dark  cells  (epithelioma  with  dark 
cells),  others  with  pale  cells — hypernephroma  malignum. 

150 


Adenoma. 


Kidney. 


Fig.  65.— Benign  hypernephroma. 

Stained  with  hematoxylon  and  eosin. 

A  small  sulphur  yellow  encapsulated  benign  tumor  unexpectedly 
found  at  autopsy. 

A.— Separation  between  the  tumor  and  the  renal  parenchyma, 
magnified  80  diameters. 

E.—Spongiocytic  cells  of  the  neoplasm  magnified  450  diameters. 


151 


NORMAL  TESTICLE. 

Testis  of  a  Dog. 

A  section  perpendicular  to  the  long  axis  of  the  testis  with  its 
epididymis  and  surrounded  by  the  tunica  vaginalis  (Fig.  66,  A). 

The  Testicle.  —  i.  The  seminiferous  tubules  (shown  in  the 
lower  part  of  drawing,  Fig.  66,  B)  are  limited  by  a  basement 
membrane  upon  which  are  placed  two  principal  types  of  cells 
arranged  in  several  layers.  Some  stain  deeply  and  show  a 
distinct  contour  and  very  distinct  nuclei.  They  are  the  cells 
of  Sertoli,  very  well  shown  here  (dog's  testis),  but  a  great  deal 
less  distinct  in  human  tissue.  They  are  recognized  by  their 
somewhat  peculiar  nuclei  flanked  by  a  nucleolus  and  juxta- 
nuclear  bodies.  These  are  the  so-called  supporting  cells. 

The  other  cells,  varying  according  to  the  layer  examined, 
belong  to  the  seminal  line  and  include  several  strata  passing 
from  the  periphery  to  the  lumen  of  the  tubule. 

(a)  The  spermatogonia,  rounded  voluminous  cells  with  large 
nuclei,  in  direct  contact  with  the  basement  membrane. 

(b)  The   spermatocytes,   cells  whose    nuclei  show  numerous 
mitotic  figures  indicating  cellular  activity. 

(c)  The  spermatids,  a  great  deal  smaller,  with  large  nuclei 
and  very  dense  protoplasm. 

(d)  The  spermatozoa,  elongated  cells  with  a  swelling  at  one 
end  (head)  and  a  caudal  membrane  (tail). 

2.  Between  the  seminiferous  tubules  a  mass  of  large  cells 
with  finely  granular  protoplasm  can  be  seen.     These  are  the 
interstitial  cells  which  seem  to  play  a  role  in  the  internal  secre- 
tion of  the  organ. 

3.  The  intermediate  zone,  which  separates  the  seminiferous 
tubules  from  the  tubules,  of  the  epididymis,  contains  the  vessels 
of  the  organ  and  its  ducts  are  lined  with  cubical  epithelium. 

The  Epididymis. — The  tubules  of  the  epididymis  are  com- 
posed of  a  rather  thick  basement  membrane,  upon  which  is 
arranged  a  single  layer  of  cylindrical  epithelium  with  pale 
protoplasm,  and  vibratory  cilia  that  show  very  well.  In  the 
center  of  the  lumen  are  collections  of  the  spermatic  secretion 
in  which  spermatozoa  can  be  seen. 

The  structure  of  the  seminiferous  tubules  with  their  stratified 
epithelium  and  highly  specialized  cells  easily  enables  them  to 
be  differentiated  from  those  of  the  epididymis. 


152 


Epididy- 
mis. 


Tunica 
albuginia. 


Testis. 


Epididymis. 


Body  of 
Highmore. 

Testicle. 


Basement 
membrane. 

Epithelial  cells 
with  vibratory 
cilia. 

Spermatozoa. 


Vessel. 


Straight  tubules 
or  ducts. 


Spermatogonia. 
Spermatids. 

Spermatozoa. 
Interstitial  cells. 


Fig.  66. — Normal  testis  of  a  dog. 
Stained  with  hematoxylon  and  eosin. 

A. —  Transverse  section  of  the  entire  testis  and  epydidymis  seen 
under  a  slight  magnification. 

E.—Part  of  A  included  in  the  square,  magnified  200  diameters, 
and  showing  the  epididymis  above  and  the  testis  below. 


153 


TUBERCULOSIS  OF  THE  TESTIS. 

Diagnosis  of  the  Organ.  —The  drawing  represents  a  group  of 
tubules  limited  by  a  fairly  thick  lamina  of  connective  tissue 
and  lined  on  the  inside  by  a  stratified  epithelium  in  a  number 
of  layers,  which  a  high  power  shows  to  be  composed  of  elements 
characteristic  of  the  testis,  and  of  its  seminiferous  tubules. 
None  of  the  tubes  has  the  structure  characteristic  of  the  epi- 
didymis.  The  tissue  then  includes  only  the  testis. 

Diagnosis  of  the  Lesion.  —The  tubules  are  more  widely  sepa- 
rated and  less  numerous  than  normal.  At  certain  points 
(upper  left-hand  portion  of  the  drawing)  the  glandular  ele- 
ments of  the  organ  have  almost  completely  disappeared  and 
their  place  is  taken  by  a  new  combination  which  upon  careful 
examination  can  be  recognized  as  that  of  the  miliary  tubercle. 
That  is  to  say: 

1.  A  giant  cell  centrally  situated  and  recognizable  by  its 
acidophilic  cytoplasm  and  the  coronet  of  peripherally  arranged 
nuclei. 

2.  The  epithelioid  cells  surrounding  the  giant  cell  with  their 
usual  transparent  protoplasm  and  elongated  nuclei. 

3.  The  lymphoid  cells  more  deeply  colored. 

Elsewhere — in  the  interiors  of  the  seminiferous  tubules 
themselves— miliary  tubercles  may  be  found  with  similar 
giant  cells  in  the  centers,  epithelioid  cells  around  them  and 
seemingly  derived  from  the  cells  of  the  seminiferous  series 
by  metaplasia.  There  is  no  caseation.  It  is,  therefore,  an 
early  tuberculosis  in  which  the  cheesy  change  has  not  had  time 
to  develop. 

Between  the  seminiferous  tubules  the  inflammatory  elements 
are  mostly  of  the  lymphoid  type;  some  are,  however,  epithelioid. 

As  a  contingent  lesion  the  thickness  of  the  basement  mem- 
brane is  to  be  noted.  In  this  case  it  is  very  distinct  and  the 
modification  of  the  seminal  cells,  which  lose  their  differentia- 
tion, tend  to  give  it  an  undifferentiated  aspect. 

Resume. — An  inflammatory  lesion  of  the  testis  of  tuberculous 
type— tuberculosis  of  the  testis.  Most  frequently  these  lesions 
are  associated  with  similar  ones  in  the  epididymis— orchi- 
epididymitis. 


154 


Tubercu- 
lous zone. 


Giant  cell 
in  the 
center  of 
a  seminif- 
erous 
tubule. 
Giant  cell. 


Epithe- 
lioid  cell. 
Lymphoid 
infiltra- 
tion. 

Necrotic 
vessels. 


Seminif- 
erous 
tubules 
with 

thickened 
walls. 


Fig.  67. — Tuberculosis  of  the  testis. 
Stained  with  hematoxylon  and  eosin.     Magnified  200  diameters. 

Tuberculous  testis  of  an  adult,  removed  at  operation.  The 
seminiferous  tubules  still  show  distinctly  in  the  lower  part  of  the 
drawing;  miliary  tubercles  are  seen  above. 


155 


CANCER  OF  THE  TESTICLE. 

Seminal  Epithelioma :  Seminoma. 

Diagnosis  of  the  Organ. — When  the  drawing  is  examined 
with  a  low  power  it  is  found  to  be  polymorphic  and  requires 
to  be  separately  studied  in  its  various  parts.  From  above 
downward  three  different  portions  can  be  noted: 

The  zone  A  can  easily  be  recognized  as  the  testicle  with  its 
seminiferous  tubules,  showing  their  usual  stratification  and 
cellular  elements  of  the  seminal  series — spermatogonia,  sper- 
matocytes  in  division  and  spermatozoa.  There  is  no  trace  of 
the  epididymis. 

The  zone  B  contains  an  enormous  mass  of  bluish  cells  com- 
pressed one  upon  another.  At  first  view  these  recall  the 
appearance  of  lymphocytes  and  seem  to  be  of  inflammatory 
nature  and  more  or  less  conjunctivo-vascular. 

Diagnosis  of  the  Lesion.— Under  a  higher  magnification, 
and  provided  that  the  fixation  of  the  tissue  was  good  to  begin 
with,  these  cells  show,  through  their  peripheral  layer  of  pale 
protoplasm  and  large  nuclei,  their  probable  derivation  from 
those  of  the  seminal  line.  Elsewhere  (left-hand  side  of  the 
drawing)  the  transformation  of  the  seminiferous  tubules  into 
these  masses  of  pseudolymphoid  cells  can  be  followed:  the 
tubes  seem  to  melt,  the  basement  membrane  disappears  and 
the  epithelial  cells  mix  with  the  neighboring  stroma.  Thus  is 
conceived  to  take  place  the  transformation  of  the  seminiferous 
tubule  and  the  origin  of  a  tumor  which  JbearsJ,tfie  name  semi- 
noma.  Elsewhere,  between  the  seminiferous  or  cancerous 
tubules,  there  are  extensive  hemorrhagic  areas  such  as  are  of 
frequent  occurrence  in  these  tumors. 

The  zone  C  is  separated  from  the  preceding  by  a  thick  band 
of  connective  tissue. 

It  is  formed  of  very  fine  fibrillae  with  scattered  nuclei,  or  may 
be  formed  of  a  layer  of  homogeneous  tissue  recalling  edematous 
fluid.  In  the  substance  of  this  mucous  (myxoid)  stroma  there 
are  elongated  nuclei  and  cystic  spaces,  sometimes  empty,  some- 
times filled  with  edematous  fluid,  lined  with  epithelial  cells 
comparable  to  those  of  the  cell  nests  described  above.  This 
appearance  of  the  tumor  with  its  hyaline  stroma  and  cystic 
spaces  is  entirely  atypical. 

Resume. — Malignant  tumor  or  cancer  of  the  testicle.  In  the 
least  modified  parts  one  recognizes  a  tumor  of  seminiferous 
origin — seminoma. 

156 


Seminif- 
erous 
tubule. 


Cancerous 
transfor- 
mation of 
the 

tubules. 
Inter- 
stitial 
hemor- 
rhage. 


Semin- 
oma. 


Connec- 
tive tissue 
partition. 

Epithe- 
lial cell 
nests. 
Mucoid 
strom  a. 

Cystic 
'cavity. 


rJHB  ^K 


•i:  &*:•**>  ^%-f  "• 

_  3&, '  '*" 'X*  .'- • '  •& .* 

./>*'';' '  j®..?"* "j&ty-"f: 
'  :'^        ^^^3* 


&^$^^'-^\'.   '  •-  ••••^^'••^f^'^^T^' 

P5eiSv-i  ?/'^.' 
iTi^-r*^^^^ 


Fig.  68. — Seminoma  of  the  testis. 


Normal 
seminif- 
erous 
tubules. 


B 


Semin- 
oma. 


Atypical 
epithe- 
lioma 
(mucoid) , 


Stained  with  hematoxylpn  and  eosin.     Magnified  50  diameters. 

.,".  'A  rdpidly  growing  tumor  surgically  removed  from  a  man,  aged 
fifty  years.  The  drawing  shows  two  different  appearances  of 
cancer  of  the  testis.  At  the  upper  part  the  "seminoma"  is  shown 
with  still  recognizable  seminiferous  tubules;  below  the  tumor  has 
become  atypical  and  myxoid  through  degeneration  of  the  stroma. 


157 


HYPERTROPHY  OF  THE  PROSTATE. 
Adenoma  of  the  Prostate. 

Diagnosis  of  the  Organ. — The  tissue  has  a  glandular  appear- 
ance. The  acini  limited  on  the  outside  by  a  delicate  basement 
membrane  (condensation  of  the  connective-tissue  stroma)  are 
lined  by  a  single  layer  of  cubical  epithelium.  The  lumen  is 
filled  with  a  finely  granular  substance:  the  prostatic  fluid 
coagulated  by  the  reagents.  In  the  interior  of  some  of  the  acini 
there  are  peculiar  formations  of  an  ovoid  form,  and  apparently 
made  up  of  concentric  stratifications  of  some  amorphous 
material— protein  concretions,  corpora  amylocia,  or  sympexions, 
of  the  prostate.  Some  of  the  narrow  spaces  are  excretory  ducts 
of  the  gland. 

The  stroma,  which  is  very  important,  is  composed  of  pale 
connective  tissue  with  numerous  smooth  muscle  fibers,  appear- 
ing as  reddish  stripes  upon  the  rose-pink  background  of  the 
connective  tissue.  These  fibers  also  differ  from  the  connective 
tissue  through  their  elongated  nuclei  swollen  at  the  ends. 

The  glandular  acini,  the  sympexions  and  the  vascular  con- 
nective tissue  stroma  enable  the  diagnosis  of  the  prostate  gland 
to  be  made. 

Differential  Diagnosis. —The  mammary  gland  is  the  only 
organ  with  which  the  prostate  can  be  confused,  and  is  to  be 
differentiated  through  its  acini  in  which  there  is  a  double  row 
of  epithelial  cells  (myoepithelial  cells),  its  stroma  rich  in  adipose 
vesicles  and  the  absence  of  muscular  fibers  in  the  stroma. 

Diagnosis  of  the  Lesions. — The  chief  characteristic  is  the 
great  irregularity  of  the  acini.  In  many  places  there  are  veri- 
table microcysts  lined  with  flattened  epithelium.  In  propor- 
tion as  the  cavities  are  distended  the  epithelial  lining  is  flattened 
until  finally  it  may  resemble  endothelium. 

In  certain  of  the  acini,  as  in  the  center  of  the  drawing,  the 
epithelium  becomes  stratified,  and  even  sends  little  vegetations 
into  the  interior  of  the  cavity.  Such  epithelial  proliferation, 
limited  to  the  tubes,  belong  to  the  variety  of  benign  glandular 
tumors  known  as  adenoma. 

The  stroma,  equally  hyperplastic,  includes  numerous  smooth 
muscular  fibers  and  connective- tissue  fibers. 

Resume.— An  adenoma,  or  benign  tumor,  of  the  prostate 
gland,  a  condition  called  in  the  clinic  hypertrophy  of  the  prostate. 


158 


Sympex- 
ion  in  the 
interior  of 
a  cyst. 


Connec- 
tive tissue 
stroma. 

Smooth 

muscle 

fibers. 


Normal 
acini. 


Cyst. 


Fig.  69.— Hypertrophy  of  the  prostate  gland. 
Stained  with  hematoxylon  and  eosin.     Magnified  30  diameters. 

A  portion  of  the  hypertrophied  prostate  surgically  removed  from 
a  man  aged  fifty-five  years.  Numerous  microscopic  cysts  are 
formed  from  the  dilatation  of  the  prostatic  glandular  acini.  In 
some  the  epithelium  is  proliferating.  Few  or  no  ducts  are  seen. 
Smooth  muscular  fibers  can  be  seen  in  the  stroma. 


159 


EPITHELIOMA  OF  THE  PROSTATE. 

Diagnosis  of  the  Organ.— This  is  scarcely  possible  to  make 
unless  there  are,  in  some  part  of  the  section,  prostatic  acini  with 
sympexions  and  smooth  muscle  fibers  in  the  stroma. 

Diagnosis  of  the  Lesion.— The  greater  part  of  the  drawing 
(lower  part  of  the  drawing,  Fig.  70)  has  a  very  different  appear- 
ance from  that  of  the  prostate  gland.  Everywhere  are  groups 
of  dark  staining  epithelial  cells  arranged  more  or  less  regularly 
in  strands  that  lose  themselves  in  the  depths  of  a  dense  con- 
nective tissue.  Some  of  the  groups  vaguely  recall  the  appear- 
ance of  acini,  but  the  architectural  confusion  is  marked. 

In  the  intermediate  zone,  that  part  of  the  drawing  between 
the  more  healthy  part  and  the  cancer,  one  can  see  the  trans- 
formation of  the  glandular  into  the  neoplasmic  formation.  At 
certain  points  the  glandular  epithelium  proliferates  and  finishes 
by  rupturing  the  basement  membrane  of  the  acinus  and  dis- 
seminating its  cells  in  the  stroma.  Even  in  the  part  of  the 
section  described  as  more  healthy,  one  can  see  at  various 
points  the  neoplasmic  transformation  of  the  glandular  acini. 

The  muscular  and  connective  tissue  of  the  gland  shows  very 
distinctly  between  the  tubules. 

Schematically  the  section  can  be  divided  into  three  portions 
or  zones  which  correspond  to  three  different  stages  in  the  devel- 
opment of  the  tumor. 

Zone  A ,  where  the  gland  is  nearly  healthy,  some  of  its  tubules 
beginning  to  proliferate;  the  beginning  of  the  development  of 
the  tumor. 

Zone  B,  in  which  the  cancer  is  developed.  It  assumes  the 
form  of  a  typical  epithelioma,  that  is  to  say,  the  arrangement  of 
the  glandular  elements  in  acini  is  preserved  for  the  most  part. 

Zone  C,  in  which  the  tumor  is  infiltrating.  Here  it  has 
become  entirely  atypical  because  of  its  degree  of  malignancy. 
It  is  impossible  here  to  determine  from  what  type  of  epithelium 
the  tumor  is  derived. 

Resume.— An  epithelioma  developed  from  the  prostate 
gland,  comparable  to  what  is  observed  in  the  breast— typical 
epithelioma  in  parts,  atypical  epithelioma  elsewhere. 


160 


Sub- 
normal 
prostate. 


Normal 

glandular 

acini. 


Adeno- 
matous 
acini. 
Acini 
undergo- 
ing 

cancerous 
transfor- 
mation. 
Smooth 
muscle 
fiber. 


Cancer 
masses. 


Fig.  70. — Cancer  of  the  prostate. 
Staining  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

The  tissue  was  operatively  removed  from  a  man  aged  seventy 
years.  In  the  upper  part  A,  the  structure  of  the  prostate  is  still 
recognizable.  In  the  middle  part  B,  the  neoplasmic  development 
is  beginning.  In  the  lower  part  C,  the  cancer  is  well  developed 
and  is  recognized  either  as  atypical  acini  with  thickened  epithelial 
linings  or  as  atypical  epithelial  cell  infiltration. 


ii 


161 


NORMAL  OVARY. 

Ovary  of  a  Cat. 

The  section  embraces  almost  the  entire  organ  and  is  com- 
posed of  a  rather  uniform  tissue,  paler  at  the  center  and  darker 
about  the  borders.  Each  portion  requires  separate  study. 

1.  In  the  central  zone— the  medullary  portion— the  matrix  is 
composed  of  an  abundant  connective  tissue,  peculiarly  rich  in 
cells    and,    therefore,    of   an    embryonal    type — fibroblastic — 
through  which  pass,  in  serpentine  fashion,  numerous  blood- 
vessels—some of  which  are  cut  transversely,  some  longitudinally. 
The  veins  among  them  can  be  recognized  by  their  flattened 
condition,  the  arteries  by  their  rounded  sections.     There  are 
also  a  great  number  of  capillaries. 

2.  The  peripheral  layer — cortical  zone — includes  an  epithelial 
covering  composed  of  cells  resting  upon  a  dense  stroma  in  which 
appear  numerous  clear  dots— enormous  cells  almost  visible  to 
the  naked  eye — the  ovules  characteristic  of  the  ovary. 

The  surface  epithelium,  or  germinal  epithelium,  is  composed 
of  cells  of  cuboidal  form  and  rests  directly  upon  the  subjacent 
stroma.  At  various  points  it  grows  down  into  the  depths  of 
the  tissue  in  the  form  of  peculiar  invaginations,  the  cell  cords  of 
Valentine- Pflueger,  which  give  origin  to  the  primordial  follicles. 
Each  of  these  follicles  is  formed  of  a  protoplasmic  mass  with 
a  central  nucleus  and  is  limited  externally  by  an  intercellular 
layer.  The  primordial  follicles  are  distributed  in  the  zone 
immediately  beneath  the  germinal  epithelium. 

More  deeply  the  Graafian  follicles,  or  ovisacs,  are  developed 
from  the  primordial  follicles.  Each  appears  as  a  cavity  filled 
with  a  finely  granular  substance  —  liquor  folliculi;  at  the 
periphery  there  is  a  thick  membrane— the  zona  pellucida;  in 
the  center,  according  to  the  thickness  of  the  section,  a  very 
large  nucleus,  the  germinal  vesicle,  provided  with  a  very  large 
nucleolus — the  germinal  spot.  At  the  periphery  of  the  ovisac 
there  are  cells  more  or  less  polygonal  in  shape,  forming  a  thick 
investiture  of  concentric  formation — the  membrana  granulosa. 

The  ripening  of  the  ovules  in  the  ovisacs,  or  Graafian  follicles, 
takes  place  from  the  time  of  puberty  to  the  menopause  (ow- 
genesis).  At  the  time  of  each  menstrual  period  an  ovule, 
arrived  at  maturity,  ruptures  its  protecting  membrane,  escapes 
from  the  follicle  and  is  caught  in  the  infundibuliform  extremity 
of  a  Fallopian  tube  where  it  is  either  fertilized  by  a  spermatozoon, 
or  eliminated  externally  with  the  menstrual  blood.  That 
which  remains  of  the  ovisac  after  its  rupture  forms  the  corpus 
luteum. 

162 


Pfliiger's 
tubes. 


Stroma. 


Ovisac. 

Mem- 
brana 
granule 


Ovisac  cut 

tangenti- 

ally. 


Medul- 
lary 
stroma. 


Fig.  71. — Normal  ovary. 
Stained  with  hematoxylon  and  eosin. 

Ovary  of  an  adult  cat.  A  shows  the  entire  organ  magnified  3 
diameters.  B  shows  the  fragment  of  the  cortical  substance  within 
the  square  in  A,  magnified  100  diameters.  It  shows  the  details 
of  cortical  structure  above  and  of  medullary  structure  below. 


Artery. 


163 


FIBROUS  CORPUS  LUTEUM. 

Senile  Ovary. 

The  section  is  made  perpendicularly  to  the  long  diameter  of 
the  ovary  (A). 

Diagnosis  of  the  Organ. — This  is  attended  with  some  diffi- 
culty, but  can  be  arrived  at  by  observing  the  division  of  the 
structure  into  the  central  or  medullary  zone  rich  in  vessels, 
continuous  with  the  pedicle  of  the  organ  and  the  peripheral 
zone,  or  cortex. 

In  the  cortex  there  are  few  or  no  Graafian  follicles,  but  there 
are  numerous  larger  structures  visible  even  to  the  naked  eye; 
the  corpora  lutea,  with  an  undulating  outline;  specific  forma- 
tions of  the  ovary  which  enable  the  organ  to  be  recognized. 

If  the  section  be  examined  under  a  higher  magnification  the 
germinal  epithelium,  which  usually  covers  the  surface  of  the 
ovary,  will  be  found  to  have  almost  entirely  disappeared. 
This  atrophied  epithelium  no  longer  dips  down  into  the  stroma, 
and  there  is  an  entire  absence  of  primordial  follicles  or  ovisacs. 
The  cortical  substance  below  is  no  longer  composed  of  fibro- 
blastic  connective  tissue.  A  little  lower  down  the  homogeneous 
masses  of  the  corpora  lutea  are  found.  Each  is  formed  of  an 
undifferentiated  material,  a  veritable  cicatricial  mass  in  the 
depths  of  which  are  some  fine  strands  of  connective  tissue  with 
nucleated  cells.  These  are  the  corpora  albicantes,  resulting 
from  the  sclerosis  and  hyaline  transformation  of  the  corpora 
lutea  of  menstruation.  In  consequence  of  their  retraction  and 
atrophy  these  elements  undergo  characteristic  transformations. 

Elsewhere  (Fig.  72,  C)  a  different  type  of  the  corpus  luteum, 
younger,  much  more  rare  in  senile  ovaries,  is  formed  of  poly- 
hedral cells  with  pale  granular  protoplasm  (lutein  cells),  with 
large  nuclei  arranged  about  the  bloodvessels— an  arrangement 
that  recalls  the  structure  of  the  glands  of  internal  secretion, 
especially  the  adrenal. 

The  cortical  stroma  is  composed  of  spindle-shaped  connective- 
tissue  cells  (fibroblasts)  arranged  in  whorls. 

In  the  most  vascular  p^art  of  the  organ  (medullary  substance) 
there  are  many  bloodvessels  in  a  state  of  hyaline  degeneration. 

Resume.— The  disappearance  of  the  germinal  epithelium, 
the  ovules  and  the  follicles  and  the  presence  of  cicatricial 
corpora  lutea  and  vessels  with  hyaline  walls,  in  the  absence  of 
any  signs  of  pathological  change,  lead  to  the  conclusion  that 
the  diagnosis  of  senile  ovary  is  justified. 

164 


Corpora  fibrosa. 


Vascular  / 
pedicle. 


Corpus 
luteum. 


Vestige  of 
germinal 
epithe- 
lium. 


Arteriole 

with 

hyaline 

wall. 


Corpus 

'                                                                                 :?llll 

fibrosum. 

^    >^^:;V^  \                                Fibro- 

,',.'»;-    -,-  ',.',','.  "-            ,i     -'I      Kl-v-tip 

'  '         :   V.         _.__:    -'"^'  ^  '•'•':*''  1/v'-':'v^',>'        "'    ]    tissue. 

Arteriole. 


Fibro- 
blasts. 


Fig.  72.— Ovary  with  corpora  fibrosa. 

Stained  with  hematoxylon  and  eosin. 

Longitudinal  section  through  the  entire  ovary  of  a  womqn,  aged 
seventy  years.  A,  entire  section  magnified  3  diameters.  ^K,  part 
of  the  cortex  magnified  100  diameters,  corresponding  to  the  part 
included  in  the  little  square  in  A.  //  shows  the  structural  details 
of  a  corpus  luteum— corpus  fibrosum.  C,  magnified  150  diameters, 
the  details  of  structure  of  a  fresh  corpus  luteum. 

165 


SCLEROCYSTIC  OVARY. 

The  section  passes  through  the  long  axis  of  an  ovary  and 
consists  of  a  swollen  part  and  a  pedicle.  With  the  naked  eye 
or  with  a  hand  lens  a  series  of  cavities  can  be  seen  arranged 
about  the  periphery  of  the  organ. 

Diagnosis  of  the  Organ. —Examination  with  a  low-power 
lens  shows  the  characteristic  elements  of  the  ovary.  That  is  to 
say: 

1.  A  connective  tissue  rich  in  fibroblasts  which  surrounds 
each  of  the  cystic  cavities  and  separates  them  one  from  another. 

2.  Here  and  there,  in  the  thickness  of  this  connective  tissue, 
are  primordial  ovules   or   Graafian  follicles   with   their  large 
central  germinal  vesicles,  the  zona  pellucida,  colored  rose  with 
the  eosin  dye  and  their  granular  membrane.     These  are  some- 
what rare  and  may  be  absent  altogether. 

3.  The  corpora  lutea  of  oval  shape.     Some  have  undulating 
outlines  and  homogeneous  structure  and  are  old,  hyaline  and 
sclerotic.    Others,  more  rare,  are  composed  of  large  pale  cells 
filled  with  fatty  granules  and  are  more  recent  corpora  lutea. 

Under  a  higher-power  magnification  one  notes  the  disappear- 
ance of  the  germinal  epithelium  which  can  only  occasionally 
be  found.  The  cysts,  variable  in  size  and  number,  contain  a 
homogeneous  mucilaginous  substance  that  colors  rose  red  with 
the  eosin  dye.  It  sometimes  entirely,  sometimes  only  partly, 
fills  the  space  on  account  of  retraction  or  fragmentation  effected 
by  the  reagents  or  manipulations  to  which  the  specimen  has 
been  subjected. 

Fig.  73  (B)  shows  the  details  of  the  structure  of  the  walls  of 
the  cysts,  as  well  as  the  mode  of  their  formation.  Below  and 
to  the  left  there  is  an  entire  small  cyst,  arising  through  trans- 
formation of  an  ovisac  with  its  granular  center,  and  its  wall 
formed  of  polyhedral  cells  in  many  layers,  derived  from  the 
membrana  granulosa  of  the  ovisac.  To  the  right,  and  above, 
is  a  portion  of  a  larger  cyst  of  which  the  wall  is  still  formed  by 
cells  arranged  in  numerous  layers.  Below,  and  to  the  right, 
in  consequence  of  further  distention  with  fluid,  the  epithelial 
lining  of  a  cyst  is  reduced  to  a  single  layer  of  flattened  cells. 

Between  these  different  cysts  the  stroma  is  represented  by 
collaginous  fibers  with  a  small  number  of  young  connective- 
tissue  cells  and  numerous  capillary  vessels  of  which  the  walls 
are  composed  of  a  single  layer  of  endothelial  cells. 

Resume. — Cystic  transformation  of  the  ovary,  or  sclerocystic 
ovary,  supposed  to  result  from  chronic  inflammation. 

166 


Cysts 


Cystic 
ovisacs. 


Stratified 
epithe- 
lium. 

Stroma. 
Flattened 
cyst  wall. 

Cyst 
contents. 


Fig.  73. — Sclerocystic  ovary. 
Stained  with  hematoxylon  and  eosin. 

Sclerocystic  ovary  of  a  woman  aged  seventy  years. 

A.— Entire  section,  cut  longitudinally  and  magnified  3  diameters. 

B. — Showing  the  structure  and  formation  of  the  cysts,  separated 
from  one  another  by  a  richly  vascular  connective  tissue.  Magni- 
fied 80  diameters. 


167 


NORMAL  UTERUS. 

A  histological  section  of  the  body  of  the  uterus,  passing 
through  the  entire  thickness  of  the  organ,  and  including  two 
distinct  zones:  the  one  quite  thick — the  muscularis,  or  muscu- 
lar wall;  the  other  much  thinner,  the  mucous  membrane,  or 
endometrium. 

Diagnosis  of  the  Organ.— Examined  under  a  low-power  lens 
(Fig.  71,  A),  the  muscularis  is  seen  to  be  composed  of  a  very 
thick  layer  of  smooth  fibers— the  greater  part  cut  transversely, 
others  longitudinally  or  obliquely.  This  gives  the  wall  of  the 
uterus  its  characteristically  plexiform  appearance. 

The  mucosa,  very  thick,  is  formed  by  a  simple  epithelium, 
lining  the  whole  interior  as  a  narrow  band  composed  of  tall 
cylindrical  cells  with  clear  slightly  acidophilic  protoplasm.  The 
nuclei  stained  deep  blue,  the  long  diameters  corresponding  to 
those  of  the  cells,  are  somewhat  close  together  at  the  basal 
portions.  By  the  ordinary  method  of  preparation  it  is  diffi- 
cult to  distinguish  the  vibratory  cilia  with  which  the  epithelial 
cells  are  provided. 

At  many  points  the  epithelium  dips  down  in  the  form  of 
"  glove  fingers"  and  penetrates  into  the  depth  of  the  subjacent 
tissue.  The  cells  lining  these  prolongations  are  of  the  same 
character  as  those  of  the  primitive  epithelial  cells  (Fig.  74,  B). 
They  are  not  active  glandular  cells  with  dense  and  finely  gran- 
ular protoplasm,  but  simple  invaginations  of  the  mucosa — 
glanduliform  invaginations. 

The  mucous  corium,  which  is  very  abundant,  is  formed 
almost  entirely  of  young  connective-tissue  cells  (fixed  cells 
and  leukocytes)  which  must  not  be  taken  as  an  indication  of 
a  pathological  state. 

The  nature  of  the  epithelium,  the  glandibuliform  depressions 
of  the  mucosa  and  the  thick  plexiform  subjacent  muscular 
layer,  are  sufficient  to  enable  the  diagnosis  of  the  body  of  the 
uterus  to  be  made  (the  neck  is  covered  with  a  stratified 
squamous  epithelium  in  its  vaginal  part). 

Differential  Diagnosis.— Sections  of  the  alimentary  canal- 
stomach,  small  intestine  and  colon — ought  not  be  confused 
with  what  has  just  been  described,  for  in  them  all  besides  the 
difference  in  the  epithelium  there  is  always  a  thick  layer  of 
connective  tissue — the  submucosa,  which  is  missing  here. 


168 


Mucosa. 


Muscle. 


Epithe- 
lium. 

Glands  of 
the  endo- 
metrium. 


Corium. 


Columnar 
epithe- 
lium. 


Corium 
with 

interstitial 
cells. 

Glanduli- 
form  de- 
pression. 


Fig.  74. — Normal  uterine  mucosa. 

A  portion  of  normal  uterus  removed  at  surgical  operation  from 
a  woman,  forty  years  of  age. 

A.— The  entire  thickness  of  the  mucosa  and  part  of  the  muscu- 
laris  magnified  20  diameters. 

B. —  The  part  included  in  the  little  square  in  A  magnified  200 
diameters,  and  showing  the  structural  details  of  the  glanduliform 
depressions. 


169 


FIBROMYOMA  OF  THE  UTERUS. 

Diagnosis  of  the  Organ. — In  actual  practice  it  is  difficult  to 
make  the  diagnosis  of  both  the  organ  and  the  lesion  if  one  is  to 
do  so  from  the  examination  of  the  sections  alone.  He  should 
always  have  information  from  the  clinic  or  autopsy  to  guide 
him.  Nevertheless  it  is  possible  to  arrive  at  a  reasonable 
degree  of  accuracy  without  it.  In  the  section  there  is  a  part 
in  which  it  is  possible  to  recognize  the  uterine  mucosa  elsewhere 
and  much  changed,  and  in  which  scarcely  any  of  the  glanduli- 
form  invaginations  exist. 

In  the  corium  young  connective-tissue  cells  and  leukocytes 
are  to  be  found  as  usual. 

Immediately  below  the  mucosa  there  is  a  narrow  band  of 
pale  connective  tissue. 

Diagnosis  of  the  Lesion. — The  greater  part  of  the  section, 
as  shown  in  the  drawing  (Fig.  75,  A),  is  formed  by  a  large 
mass  of  dark  staining  elements  arranged  in  whorls. 

Under  a  higher  power  lens  these  are  found  to  be  composed  of 
elongated  cells  grouped  in  bundles  cut  transversely,  obliquely 
and  longitudinally.  Their  dense  protoplasm  is  strongly  colored 
with  the  eosin,  and  each  shows  in  the  center  an  elongated 
nucleus  of  a  rod  shape,  not  pointed  at  the  extremities.  These 
are  unstriped  muscle  fibers  such  as  are  encountered  in  the 
thickness  of  the  uterine  wall. 

That  which  differentiates  this  muscular  tissue  from  that  of 
the  normal  uterine  wall  is  the  marked  disposition  to  occur  in 
whorls,  with  disarrangement  of  the  fibers. 

In  some  areas,  in  the  substance  of  the  muscular  mass,  rose- 
red  patches  are  formed  by  connective  tissue  rich  in  collagen, 
with  fusiform  nuclei  a  little  shorter  than  the  muscle  nuclei— 
fibrous  fasciculi. 

Such  an  appearance  corresponds  with  that  of  a  benign  tumor 
— a  myoma  or  fibromyoma — according  to  the  proportion  of  con- 
nective to  muscular  tissue  present. 

With  greater  precision,  the  tumor  is  a  submucous  intraparietal 
myoma,  easily  enucleable. 

Resume.— A  benign  tumor— a  uterine  fibromyoma— developed 
in  the  wall  of  the  uterus  and  formed  chiefly  of  unstriated  mus- 
cular fibers. 

Such  common  muscular  tumors  of  the  uterus  frequently  un- 
dergo a  malignant  degeneration  and  terminate  in  myosarcoma 
with  frequent  interstitial  hemorrhage,  monstrous  nuclei,  necrotic 
zones  and  metastases. 

170 


Pseudo- 
glandular 
crypts. 

Vessels. 


B 

Smooth 
muscle 
fibers  cut 
trans- 
versely. 


Smooth 
muscle 
fibers  cut 
longitu- 
dinally. 


Fig.  75. — Fibromyoma  of  the  uterus. 
Stained  with  hematoxylon  and  eosin. 

Intramural  fibromyoma  of  a  uterus  which  showed  in  addition 
an  enormous  submucous  sloughing  fibromyoma.  Removed  at 
operation. 

A.— The  uterine  wall  with  the  enucleable  intramural  fibromyoma, 
magnified  25  diameters. 

B. — A  portion  of  the  tumor  magnified  200  diameters. 


171 


CANCER  OF  THE  BODY  OF  THE  UTERUS. 

Diagnosis  of  the  Organ.— It  is  extremely  difficult  if  not 
impossible  to  say  what  organ  the  section  ec^es  from.  The 
diagnosis  has  to  be  presumptive. 

The  greater  part  of  the  tissue,  upon  careful  examination, 
proves  to  consist  of  a  musculo-connective-tissue  matrix,  par- 
ticularly rich  in  smooth  muscle  fibers  which  makes  us  think 
of  the  uterus,  the  bladder  or  the  prostate.  The  abundance 
and  disorderly  arrangement  of  the  pgeudoglandular  formation 
with  which  the  tissue  abounds,  some  of  which  are  united  while 
others  are  separate,  gives  the  impression  of  a  neoplasm— a 
tumor  of  the  type  of  columnar  glandular  epithelium. 

Diagnosis  of  the  Lesion.— The  spaces,  or  epithelial  cavities, 
are  lined  with  tall  cylindrical  epithelial  cells  with  abundant 
protoplasm,  and  nuclei  also  elongated  and  deeply  stained. 
They  are  arranged  parallel  and  in  several  layers,  thus  constitut- 
ing a  stratified  epithelium.  Under  a  higher  power  magnifica- 
tion (Fig.  76,  B)  the  cells,  which  line  the  spaces  are  found  to 
retain  their  tiny  filaments— vibratory  cilia.  In  a  nest  full  of 
epithelial  cells  the  cylindrical  form  may  be  lost,  the  arrangement 
in  parallel  rows  has  disappeared  and  the  cells,  side  by  side, 
sometimes  contain  nuclei  of  monstrous  size  with  abnormal 
karyokinetic  figures.  Finally,  the  substance  of  the  protoplasm 
frequently  contains  little  dark  chromatin  granules  (pseudo- 
coccidia).  In  the  centers  of  the  glandular  tubules  small  masses 
of  amorphous  substance  with  more  or  less  nuclear  debris  (cellu- 
lar necrosis),  sometimes  less  altered  desquamated  epithelial 
cells  can  be  found. 

The  stroma  is  formed  of  connective  tissue  and  smooth  muscu- 
lar fibers.  The  paler  connective  tissue  is  chiefly  represented 
by  fibroblasts  with  elongated  protoplasm  and  fusiform  nuclei 
and  by  some  fixed  connective-tissue  cells. 

The  smooth  muscular  fibers  (more  deeply  stained  with  the 
red)  have  nuclei  that  are  not  pointed  at  the  ends.  There  are 
some  masses  of  round  cells  especially  formed  about  the  blood- 
vessels— small  areas  of  inflammatory  infiltration. 

Resume.— It  is  a  neoplasm  of  the  columnar  epithelial  glandu- 
lar type;  a  tumor  because  of  the  architectural  confusion  of  the 
tissues  and  a  malignant  tumor  because  of  the  atypical  character 
of  the  cells.  This  epithelial  tumor,  or  epithelioma,  is  developed 
from  the  mucosa  of  the  fundus  of  the  uterus  and  penetrates 
the  entire  thickness  of  its  wall.  The  lymphocytic  infiltration 
is  explained  by  the  fact  that  the  tumor  was  ulcerated. 

172 


Smooth 
muscle   " 
fibers. 
Vessels. 


Neoplastic  epithelial  nests. 


Pseudo- 
glandular 
prolifera- 
tion. 


Stroma. 

Inflam- 
matory 
infiltra- 
tion. 

Cancer 
cell  nests. 


Neo- 

plasmic 

acinus. 


Fig.  76. — Cylindrical  epithelioma  of  the  body  of  the  uterus. 
Stained  with  hematoxylon  and  eosin. 

A. — Section  of  a  fragment  of  the  body  of  the  uterus  taken  from 
a  part  of  the  muscular  wall  infiltrated  with  cancer  nests.  Magnified 
20  diameters. 

B. —  The  same  showing  the  pseudo glandular  appearance  of  the 
tumor  formed  of  cylindrical  cells  containing  nuclear  monstrosities. 


173 


CANCER  OF  THE  NECK  OF  THE  UTERUS. 
Epithelioma  Spinocellulare. 

Diagnosis  of  the  Organ.  — An  examination  of  the  section  under 
a  low-power  lens  enables  a  presumptive  diagnosis  to  be  made. 
The  left-hand  part  of  the  drawing  shows  a  stratified  squamous 
epithelium  supported  upon  a  musculo-connective  tissue.  The 
superficial  layers  are  not  cornified  and  the  corium  does  not 
contain  fat  cells.  It  is  then  a  Malpighian  (squamous)  mucous 
membrane.  The  arrangement  of  the  smooth  muscle  fibers 
below  the  squamous  epithelium  makes  one  think  of  the  neck 
of  the  uterus.  This,  however,  refers  to  the  vaginal  portion 
only,  for  the  neighboring  portion  of  the  isthmus  is  covered  with 
a  single  layer  of  columnar  epithelial  cells.  This  opinion, 
however,  should  be  confirmed  by  information  from  the  clinic 
or  the  report  of  the  autopsy. 

Diagnosis  of  the  Lesion. — If  the  epithelium  be  followed 
from  one  side  to  the  other  (Fig.  77,  A)  it  will  be  seen  that  the 
basal  layers  become  less  undulating  and  thicken  into  a  condi- 
tion of  acanthosis.  Further  to  the  right  the  epithelial  covering 
disappears— an  ulcer ation.  In  the  corium  there  are  epithelial 
prolongations  that  deeply  invade  the  musculo-connective  tissue 
of  the  organ.  It  is,  therefore,  a  tumor  and  a  squamous-cell 
carcinoma  of  the  vaginal  portion  of  the  neck  of  the  uterus. 

The  drawing  B  gives  the  histological  details  of  the  tumor.  It 
is  formed  of  cells  more  or  less  resembling  those  of  the  squamous 
mucous  membranes— epithelioma  Spinocellulare.  In  the  center 
of  the  drawing  there  is  a  bloodvessel— an  arteriole— whose 
tunica  musculo-elastica  is  much  thickened.  About  it  in  the 
peri  vascular  space  is  some  protoplasmic  debris,  some  of  which 
is  multinucleated.  This  is  the  debris  of  cancer  cells  which 
have  invaded  the  perivascular  lymph  spaces  and  might  have 
been  transported  to  other  parts  of  the  body.  In  the  upper 
right-hand  part  of  drawing  B  there  is  another  lymph  vessel 
stuffed  full  of  cancer  cells.  Such  invasion  of  the  lymph  vessels 
is  common  in  epitheliomas  in  general.  In  the  neck  of  the 
uterus  it  explains  the  peculiar  tendency  of  the  tumor  to  extend 
widely  and  early  reach  the  cellular  tissue  at  the  base  of  the 
broad  ligament,  especially  the  periurethral  parametrium. 

One  should  be  particular  to  notice  the  presence  of  numerous 
monstrous  nuclei  and  the  frequent  cellular  divisions  which 
evince  the  malignant  nature  of  the  tumor  and  the  tendency 
of  its  tissues  to  proliferate  and  to  degenerate. 

Resume.  —  Epithelioma  Spinocellulare  of  the  vaginal  portion  of 
the  neck  of  the  uterus. 

174 


Stratified 

squamous 

epithelium. 


Corium. 


Cancer. 

B 

Cancer 

cells  in  a 

perivascu- 

lar  lymph 

space. 


Arteriole. 


Degener- 
ated zone. 


Ulcerated 
epithe- 
lium. 


Dilated 
capillary. 

Epithelial 
columns. 


Cancerous 
lymphan- 
gitis. 


Mon- 
strous 
nuclei. 


Fig.  77. — Squamous  cell  carcinoma  of  the  neck  of  the  uterus. 

Stained  with  hematoxylon  and  eosin. 

A.—  Vaginal  portion  of  the  neck,  magnified  25  diameters. 
B.— Cancer  masses  with  nuclear  monstrosities. 

175 


ULCERATIVE  METRITIS  OF  THE  NECK  OF 
THE  UTERUS. 

Diagnosis  of  the  Organ.— This  should  be  made  by  noting 
the  simultaneous  presence  of  a  very  thick  mucosa  covered  by 
columnar  cells  and  a  muscularis  separated  from  one  another 
by  a  corium  of  a  pseudolymphoid  appearance.  These  together 
with  the  unstriated  and  plexiform  character  of  the  muscularis, 
and  the  fact  that  the  mucosa  sends  extensions  consisting  of 
young  cellular  connective  tissue  deeply  into  a  corium,  make 
the  diagnosis  of  uterus  with  certainty.  The  somewhat  disso- 
ciated appearance  of  the  muscular  fibers  makes  one  think  of 
the  neck  of  the  uterus. 

Diagnosis  of  the  Lesion. — The  section  is  drawn  under  a  low- 
power  magnification.  Fig.  78,  A,  shows  in  the  right-hand  upper 
portion  a  thick  mucosa,  in  the  depths  of  which  there  are  numer- 
ous glandular  crypts.  These  are  sometimes  cut  perpendicu- 
larly, sometimes  parallel,  and  show  as  cavities  with  sinuous 
walls.  At  the  left  of  the  section  the  mucosa  disappears;  it 
is  an  ulceration.  In  the  depths  of  the  mucosa  the  glands  are 
greatly  dilated,  forming  cysts  with  mucous  or  mucopurulent 
contents ;  these  are  called  the  cysts  or  follicles  of  Naboth.  They 
are  formed  through  the  inflammatory  obliteration  of  the  orifices 
of  the  glandular  crypts  and  are  extremely  common  in  the  uterus. 
But  a  diagnosis  of  metritis  must  not  be  made  upon  their  presence 
alone.  Under  a  higher  magnification  (Fig.  78,  B)  the  details 
of  the  inflammatory  lesion  of  the  corium  can  be  studied.  The 
epithelium  consists  of  tall  cylindrical  cells,  covering  the  surface 
of  the  neck  and  descending  deeply  into  the  glandular  depres- 
sion. The  mucous  corium  is  formed,  in  the  normal  state,  of  a 
stroma  full  of  young  connective-tissue  cells  of  a  pseudolymphoid 
appearance.  This  infiltration  is  strongly  emphasized  in  the 
present  case  and  at  two  points  the  cells  are  approximated  so 
as  to  form  definite  inflammatory  masses.  Going  hand  in  hand 
with  this  lymphatic  hyperplasia  there  is  an  unusual  number  of 
capillaries.  The  unstriated  muscle  shows  no  pathological 
alteration. 

Resume. — The  hypertrophy  of  the  mucous  membrane,  its 
ulceration  at  certain  points,  the  cysts,  the  infiltration  and  the 
deformity  of  the  glands  make  the  diagnosis  of  ulcerative  metritis 
of  the  neck  of  the  uterus.  Hypertrophic  subacute  metritis 
with  diffuse  glandular  and  periglandular  lesions  of  the  mucosa. 

176 


Ulceration 


Nabothian 
follicle. 


Glandular 
orifice. 


Ulceration. 


Epithe- 
lium. 
Tubular 
glands. 


Gland. 


Corium. 


Muscle. 


Inflam- 
matory 
nodule. 


Capillary. 


Corium. 


Gland. 


Fig.  78. — Ulcerative  cervical  metritis. 

Stained  with  hematoxylon  and  eosin. 

A. — Portion  of  the  section  magnified  10  diameters,  showing  the 
general  topography  of  the  structure  and  the  ulceration  of  the  mucosa. 

B.— A  glanduliform  depression  with  lesions  of  the  ulcerated 
epithelium,  of  the  corium,  and  the  inflammatory  infiltration,  magni- 
fied 150  diameters. 

12  177 


ACUTE  SALPINGITIS. 

Diagnosis  of  the  Organ. — A  circular  section  (Fig.  79,  A)  with 
irregular  spaces  in  the  center.  Under  a  low-power  lens  the 
peripheral  part  of  the  section  is  found  to  be  made  up  of  inter- 
lacing smooth  muscle  fibers  cut  longitudinally  and  transversely. 
Here  and  there  are  dark  spots.  Inside  of  the  muscular  coat  is 
a  mucosa  with  its  multiple  tubules  deformed  and  ramifying 
in  so  peculiar  a  manner  as  to  give  the  impression  of  a  veritable 
labyrinth— an  appearance  that  is  only  to  be  encountered  in 
the  infundibuliform  Fallopian  tube  with  its  multiple  mucous 
folds.  In  this  case  the  secondary  and  even  the  tertiary  folds 
have  lost  some  of  their  epithelial  covering  as  the  result  of 
inflammation,  and  have  become  soldered  together.  It  is  thus 
that  the  peculiar  diminished  and  divided  appearance  of  the 
interior  of  the  tube  is  brought  about. 

Diagnosis  of  the  Lesion  (Fig.  79,  B).— The  muscularis, 
which  is  covered  on  the  outside  by  a  peritoneal  endothelium 
which  is  imperfect,  is  composed  of  bundles  of  fibers  indefinitely 
mixed  together.  The  normal  arrangement  in  two  layers,  one 
circular  and  one  longitudinal,  does  not  obtain  here,  or,  at  least, 
is  not  visible. 

In  the  entire  thickness  of  the  walls,  but  especially  near  to  the 
external  surface,  there  are  numerous  dilated  vessels,  and  about 
them  an  inflammatory  infiltration  composed  of  round  cells— 
leukocytes.  These  same  cells  are  separately  disseminated 
throughout  the  smooth  muscle  tissue  of  the  wall. 

Further  inside  the  mucosa  is  very  much  altered.  The  vibra- 
tory cilia  have  entirely  disappeared.  All  that  can  be  seen  is 
that  the  epithelium  on  the  mucosa  occurs  in  a  single  layer 
and  is  frequently  interrupted  through  desquamation.  This 
appearance  is  particularly  distinct  in  the  spaces  or  pseudo- 
glandular  cavities  which  result  from  the  adhesion  of  the  various 
folds.  In  the  interior  of  these  cavities  degenerated  poly- 
nucleated  leukocytes  are  mixed  with  the  desquamated  epithe- 
lium, all  bathed  in  a  serous  fluid  which  in  case  of  obstruction 
can  occasion  the  distention  of  the  tube  and  the  occurrence  of 
the  condition  known  as  pyosalpinx. 

Resume. —Acute  inflammation  with  preponderating  lesions 
in  the  mucosa— acute  salpingitis.  By  special  methods  of 
staining  it  may  be  possible  to  demonstrate  the  presence  of 
microorganisms,  the  most  frequent  and  specific  being  the 
gonococcus;  less  specific  the  more  common  microorganisms  of 
suppuration,  the  staphylococcus  or  the  streptococcus. 

178 


Muscular  wall. 
Infiltration. 
Pseudo-glands. 


Circular 
muscle 
fibers. 


Connec- 
tive tissue 
fibers. 


Pseudo- 
glands    .}  ..$ 
containing 
pus. 


PUS.    m 


Inflam- 
matory 
infiltra- 
tion. 


Circular 

muscle 

fibers. 


Longi- 
tudinal 
muscle 
fibers. 


Pseudo- 
gland. 

Granula- 
tion tissue 
replacing 
the 
mucosa. 


Fig.  79.— Acute  gonococcic  salpingitis. 
179 


FIBROADENOMA  OF  THE  BREAST. 

Diagnosis  of  the  Organ.— At  the  right-hand  part  of  Fig.  80,  A, 
there  is  a  connective  tissue  in  which  are  a  number  of  small 
duct-like  structures,  some  of  which  are  grouped  as  acini  about 
little  ducts  (galactophorous  ducts)  which  appear  as  small 
slits  or  crevices  in  the  tissue,  each  lined  with  epithelium.  There 
are  also  occasional  groups  of  fatty  vacuoles.  This  arrangement 
of  acini  in  groups  about  galactophorous  ducts,  in  a  stroma 
fibrous  and  fatty,  is  characteristic  of  the  mammary  gland. 

Differential  Diagnosis. — One  single  other  organ  can  be  mis- 
taken for  the  mammary  gland — that  is  the  prostate.  But  in 
its  stroma  there  is  no  fatty  substance,  but  instead  an  admixture 
of  smooth  muscle  fibers  and  in  the  acini  there  are  nitrogenous 
concrements  or  sympexions.  Moreover,  under  a  high  power  it 
is  easy  to  recognize,  in  well-fixed  tissue,  two  rows  of  nuclei, 
as  there  are  both  glandular  cells  and  myoepithelial  cells. 

Diagnosis  of  the  Lesion. — One  cannot  help  being  struck  by 
the  architectural  confusion  of  the  remaining  half  of  the  drawing 
(left-hand  portion  of  Fig.  80,  A).  There  are  no  acini;  every- 
where there  is  a  starred  appearance,  formed  by  attenuated 
ductules,  the  extremities  of  which  are  variously  evaginated  and 
exvaginated.  The  lumina  are  lined  by  an  epithelium  that 
appears  to  be  partly  desquamated  on  account  of  bad  fixation. 
These  structures  are  derived  from  the  proliferated  acini.  A 
matrix  of  a  special  variety  of  connective  tissue  surrounds  and 
separates  the  glandular  formations.  The  most  internal  part  of 
this  tissue,  with  a  pale  tint,  has  undergone  mucoid  degenera- 
tion. The  proliferation  and  development  of  this  tissue,  which 
has  crowded  out  the  acini  and  compressed  their  walls,  explains 
in  large  measure  the  peculiar  appearance  of  its  epithelial  struct- 
ures. At  the  periphery  of  the  neoplastic  nodule,  and  separating 
it  from  the  mammary  tissue  proper,  there  is  a  delicate  connec- 
tive-tissue wall  that  definitely  circumscribes  the  neoplasm. 

It  is  to  be  noted  that  the  mammary  tissue  proper  does  not 
have  a  normal  appearance;  the  acini  are  small  and  compressed 
in  a  sclerosed  matricial  tissue. 

Resume. — Tumor  of  the  breast  following  the  abnormal 
development  and  proliferation  of  the  connective- tissue  stroma; 
a  benign  tumor,  or  fibroadenoma:  (i)  Because  of  its  distinct 
circumscription  and  independence  from  the  organ  in  which  it 
develops;  (2)  because  the  basement  membrane  is  not  broken 
through  so  that  processes  of  the  epithelium  can  escape  into 
the  stroma;  (3)  because  the  connective  tissue  is  of  adult  type, 
with  few  cells. 

180 


Connec- 
tive tissue 
capsule 
of  the 
tumor. 


Mammary 
acini  in 
chronic 
mastitis. 
.  Sclerosed 
stroma. 

Galacto- 
phorous 
duct. 


Myxoid 
surround- 
ing tissue. 

Desqua- 
mated 
epithe- 
lium. 


Mucoid 
connec- 
tive tissue. 


Fig.  80. — Pericanalicular  fibro-adenoma  of  the  breast. 
Stained  with  hematoxylon  and  eosin. 

A  benign  enucleable  tumor,  movable  beneath  the  skin,  removed 
from  the  breast  of  a  woman  aged  thirty  years. 

A.— Showing  the  line  of  separation  between  the  tumor  and  the 
breast,  magnified  12  diameters. 

B. — A  portion  of  the  tumor,  magnified  150  diameters. 

181 


CANCER  OF  THE  BREAST. 

The  drawing,  which  represents  in  its  totality  a  section  of  a 
considerable  extent  of  breast  tissue,  enables  one  to  follow  in 
a  methodical  fashion  the  mode  of  development  of  cancer  of 
the  breast. 

Toward  the  upper  right-hand  corner  of  the  drawing  (Fig. 
81,  A)  a  few  rare  glandular  acini  are  almost  lost  in  the  very 
dense  fibrous  tissue,  but  permit  one  to  recognize  the  tissue 
of  the  breast,  and  from  an  organ  affected  with  chronic  mammi- 
tis  (mastitis).  In  the  lower  right-hand  portion  of  the  section 
(Fig.  81,  A)  there  are  numerous  cystic  formations  of  varying 
size — beginning  intracanalicular  epithelioma.  Finally,  at  the 
lower  left-hand  corner  (Fig.  81,  A) there  is  an  extensive  infiltra- 
tive  mass  of  nests  and  processes,  composed  of  cells  that  color 
deeply  with  the  nuclear  stains — atypical  epithelioma. 

Let  the  different  portions  be  studied  in  detail: 

1.  Fig.  81,  B,  represents  No.  i  of  Fig.  81,  A,  drawn  under  a 
higher  power.     The  glandular  acini  are  lost  in  a  stroma  of  dense 
connective  tissue  formed  chiefly  of  collagen  fibers  with  only 
occasional  nuclei  and  few  if  any  fatty  vesicles.     The  acini  are 
dissociated,  isolated  or  extinguished  by  the  proliferation  of  the 
connective  tissue   (sclerosis).     In  the  center  there  are  longi- 
tudinal  sections   of   two   galactophorous   ducts.     The   use   of 
the  higher  power  shows  distinctly  the  characteristic  structure 
of  a  glandibular  epithelium:     cells  resting  upon  a  peripheral 
basement  membrane,  a  simple  condensation  of  the  connective- 
tissue    stroma,    but    whose    topographical    interest    from    the 
point  of  view  of  tumor  study  is  great.     If  the  structure  of  the 
mammary  acini  is  still  recognizable   their  scarcity  coincides 
with  the  density  of  the  stroma  resulting  from  a  diffuse  inflam- 
mation—chronic  mammitis. 

2.  The  following  figure  (Fig.  82,  C)  shows  the  details  of  No.  2 
of  Fig.  8 1,  A.     Here  are  larger  or  smaller  cysts,  sometimes  even 
visible  to  the  naked  eye.     The  contours  are  very  irregular  and 
the  wall  formed  of  epithelial  cells  in  numerous  layers  limited 
on  the  outside  by  the  basement  membrane.     The  cells  are  of 
the  cuboidal,  sometimes  cylindrical,  form  and  have  nuclei  of 
various  size,  rich  in  chromatin;    some  of  them  are  monstrous 
and  show  mi  to  tic  figures.     The  mucosa  that  lines  the  cysts 
grows  into  the  interior,  forming  numerous  prolongations  (in vagi- 
nations).     Sometimes  these  are  provided  with  a  connective- 
tissue  axis  that  enables  them  to  project  into  the  cavity  of  the 

182 


Cancerou 
infiltration 

No.  3- 

Zone  of 

atypical 

epithe- 

lioma. 


B 


Sclerosed 
strom  a. 


No.  i- 
$|j\    Zone  of 
chronic 
',  mastitis. 


Transi- 
tion zone. 
No.  2. 
Zone  of 
intra- 
canalicu- 
lar  epithe- 
lioma. 


Galacto- 
phorous 
duct. 


Galacto- 
phorous 
duct. 


Sub- 
normal 
acinus. 


Fig.  81. — Epithelioma  of  the  breast. 

Stained  with  hematoxylon  and  eosin. 

Cancer  of  the  breast  of  a  woman,  aged  forty-five  years,  removed 
at  surgical  operation. 

A. — The  entire  section  magnified  5  diameters. 
E.—Zone  of  chronic  fibrous  mastitis,  magnified  75  diameters. 

183 


cyst.  These  intracanilicular  invaginations  or  processes  can  take 
on  a  considerable  development.  In  the  thickness  of  their  walls 
there  may  be  innumerable  minute  cysts— secondary  intra- 
parietal  cysts.  The  cavities  contain  a  structureless  mass  of 
coagulated  material,  usually  of  a  finely  granular  nature,  in 
which  there  are  apt  to  be  numerous  desquamated  epithelial 
cells  from  the  alveolar  walls,  in  an  advanced  state  of  degenera- 
tion, with  nuclei  in  a  state  of  pycnosis. 

The  presence  of  intracanalicular  buds,  the  stratification  of 
the  epithelial  bed  and  the  numerous  atypical  cells  make  the 
aspect  of  the  tumor  very  suspicious  from  the  point  of  view  of 
malignancy.  It  can  be  already  affirmed  that  we  have  to  do 
with  an  intracanalicular  epithelioma  or  dendritic  epithelioma. 
In  order  to  confirm  the  diagnosis  one  studies  with  care  the 
condition  of  the  basement  membrane,  an  important  element 
not  only  from  the  diagnostic  point  of  view,  but  also  from  the 
point  of  view  of  prognosis.  Insomuch  as  the  basement  mem- 
brane appears  to  be  intact,  one  has  to  do  with  a  malignant 
tumor  still  limited,  with  little  chance  of  lymphatic  metastasis 
after  ablation  by  the  surgeon.  Here,  on  the  contrary,  though 
the  basement  membrane  appears  to  be  intact,  one  already 
finds  neoplasmic  cells  (cancerous  emboli)  outside  of  certain  of 
the  cysts  in  the  interior  of  the  vessels. 

3.  In  Fig.  82,  D  (No.  5  of  the  drawing  A),  the  cancerous 
infiltration  is  established.  Only  at  rare  points  does  one  find 
cystic  glandular  formations;  elsewhere  there  are  little  masses 
or  fine  strands  of  cells,  with  an  occasional  large  nest  of  cells 
distributed,  throughout  the  stroma.  Only  occasional  circular 
groupings  distinctly  recall  the  glandular  arrangement  of  the 
neoplasm — atypical  or  infiltrating  epithelioma. 

The  stroma  of  the  tumor  is  an  adult  connective  tissue 
infiltrated  with  small  round  cells  which  indicate  an  infection 
added  through  ulceration  of  the  tumor. 

Resume. — In  this  specimen  all  of  the  stages  in  the  develop- 
ment of  a  glandular  tumor  can  be  followed  from  the  precan- 
cerous  stage  (chronic  mammitis)  to  the  formation  of  an  atypical 
epithelioma.  It  ought  not  be  imagined  that  one  easily  finds, 
as  in  this  case,  all  of  these  various  stages  in  a  single  histological 
preparation  of  cancer  of  the  breast.  It  is  usually  necessary 
and,  therefore  better,  to  prepare  several  fragments  from  the 
material  removed  at  operation  in  order  to  make  the  diagnosis 
of  the  tumor. 

1S4 


Cancer 
exudate. 

Vegeta- 
tion with 
connec- 
tive tissue 
axis. 


Epithelial 
wall. 


D 

Intra- 
acinus 
epithelial 
prolifera- 
tion. 


L   Stroma. 


Ruptured 
basement 
mem- 
brane. 


Isolated 

cancer 

cells. 


Epithelial 
processes. 


Fig.  82.— Epithelioma  of  the  breast. 
Stained  with  hematoxylon  and  eosin. 

Same  case  as  Fig.  81,  magnified  75  diameters. 

C. — Zone  of  intracanalicular  epithelioma  with  cystic  formations 
and  vegetations  (point  No.  2,  Fig.  81). 

D.—Zone  of  atypical  infiltrating   epithelioma   (point  No.   3, 
Fig.  81). 

185 


HEMIPLEGIA  OF  CEREBRAL  ORIGIN. 

Descending  Degeneration  of  the  Pyramidal  Tract. 

In  order  to  be  able  to  interpret  the  sections  which  follow  and  to 
appreciate  their  lesions  it  is  indispensable  to  have  at  least  an 
elementary  idea  of  the  technic  employed  in  the  study  of  the 
pathology  of  the  nervous  system. 

The  tissues  of  the  central  nervous  system  are  fixed  in  forma- 
Jine  (10:100)  and  after  hardening  are  cut  into  sections  either 
frozen  or  after  embedding  in  celloidin  or  paraffine. 

The  staining  of  the  sections  is  achieved  through  a  variety  of 
methods  according  to  the  particular  information  that  it  is 
desirable  to  gain.  This  may  have  reference  to  the  nerve  cells, 
the  myelin  sheaths,  the  neuroglia  or  the  fibrovascular  tissue. 

The  cellular  elements  visible  in  sections  stained  with  hema- 
toxylon  and  eosin  are  particularly  well  brought  out  by  the 
method  of  Nissl  (fixation  in  alcohol  and  staining  in  polychrome 
bftie)  which  colors  the  protoplasmic  granulations  of  the  nerve 
cells  blue. 

When  it  is  desirable  to  demonstrate  the  myelin  sheaths  of 
the  nerve  fibers  and  bring  out  fresh  or  old  degeneration  of  the 
fibers  the  methods  of  Weigert,  Weigert-Pal  or  Nageotte  are 
appropriate.  The  myelin  sheaths  which  surround  the  axis- 
cylinders  are  colored  blue  by  the  method  of  Nageotte;  intense 
black  by  the  methods  of  Weigert  and  Weigert-Pal.  The  cells 
stain  badly  by  these  methods  and  appear  brown  upon  a  yellowish 
field. 

The  tracts  of  nerve  fibers  stained  intensely  black,  cut  longi- 
tudinally or  transversely  in  the  sections  and  contrasting  with 
the  brown  background  are  highly  characteristic  of  sections  of 
the  central  nervous  system  stained  by  the  methods  of  Weigert 
or  Weigert-Pal.  But  it  only  applies  to  healthy  nerve  fibers 
with  intact  myelin  sheaths.  The  degenerated  sheaths  whose 
continuity  has  been  interrupted  (Wallerian  degeneration)  do 
not  stain. 

The  employment  of  the  Weigert  method,  therefore,  result 
in  the  demonstration  of  dark  areas— healthy  nerve  tracts— and 
pale  areas— degenerated  nerve  tracts.  These  methods  are, 
therefore,  only  adapted  to  the  study  of  the  white  matter  which 
is  composed  entirely  of  nerve  fibers  and  should  not  be  employed 
when  it  is  desired  to  determine  the  condition  of  the  gray  matter 
and  nuclei.  But  care  must  be  taken  not  to  confuse  cell  aggre- 
gations, which  stain  palely,  with  fiber  degeneration,  and  the 
beginner  will  do  well  to  begin  by  assuring  himself  of  the  absence  of 

186 


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187 


cells,  and  noting  that  the  part  under  examination  corresponds 
to  some  tract  of  fibers. 

It  is  further  indispensable  to  know  the  anatomy  of  the 
different  motor  and  sensory  tracts  of  the  central  nervous  system. 

We  now  proceed  to  examine  a  series  of  sections  made  from 
different  levels  of  the  central  nervous  system  of  a  case  of  hemi- 
plegia  following  upon  a  lesion  in  the  left  cerebral  cortex. 

The  drawing  (Fig.  83)  represents  a  section  passing  through 
the  cerebral  peduncles,  sufficiently  characteristic  to  be  easy  to 
recognize.  The  general  form  of  the  section  can  be  compared 
to  a  triangle  with  rounded  corners,  the  summit  corresponding 
to  the  "tegmentum"  and  the  two  angles  to  the  two  cerebral 
peduncles.  The  tegmentum  is  posterior  and  the  crusta  anterior 
in  the  microscopic  sections. 

In  the  tegmentum  the  central  and  median  part  contains  a 
triangular  canal — the  aqueduct  of  Sylvius — which  effects  a  com- 
munication between  the  third  and  fourth  ventricles.  On  each 
side  of  the  aqueduct,  at  the  periphery  of  the  section,  is  a  pale 
oval  mass,  the  posterior  corpus  quadrigeminus,  in  which  the 
fibers  of  the  auditory  nerve  terminate,  and  which  bounds  the 
section  in  front  of  the  corpus. 

In  front  of  the  aqueduct  of  Sylvius,  a  pale  mass  of  cells  marks 
the  position  of  the  nucleus  of  the  third  pair  of  cranial  nerves 
(oculomotor),  of  which  one  sees  the  fibers  directed  forward, 
traversing  a  dark  mass  of  large  size,  the  nucleus  ruber,  and 
passing  on  to  end  in  the  inter  peduncular  space. 

The  tegmentum  is  separated  from  the  crusta  by  a  pale 
band  (not  to  be  confused  with  degeneration) ;  it  is  the  locus  or 
substantia  niger.  Behind  it  is  a  dark  band — the  median  ribbon 
of  Reil,  or  median  fillet.  In  the  foot  of  the  peduncle  the  motor 
tracts  are  arranged  as  follows:  The  internal  fifth  comprises  the 
voluntary  fasciculus  from  the  face  or  face  genicule;  the  external 
fifth,  the  fasciculus  of  Meynert;  the  middle  part  to  the  pyramidal 
tract  which  contains  all  of  the  motor  fibers  passing  to  the  pons, 
the  medulla  and  the  spinal  cord. 

Thus  far  all  of  the  described  tracts  and  nuclei  have  presented 
a  normal  appearance,  but  in  the  middle  part  of  the  foot  of  the 
left  peduncle  there  is  a  distinctly  pale  median  zone  of  degen- 
eration in  which  a  higher  power  lens  shows  no  normal  myeline 
sheaths.  This  degenerated  area  is  bounded  on  the  inner  and 
outer  sides  by  healthy  zones  and  corresponds  to  the  space 
occupied  by  the  fibers  of  the  pyramidal  tract  on  their  way  from 
the  cortex  to  the  medulla. 

188 


189 


The  drawing  (Fig.  84)  is  sharply  limited  on  the  right  and  left 
by  two  straight  lines  which  correspond  to  cuts  made  by  the 
knife  in  diminishing  the  extent  of  nervous  tissue  to  be  sectioned. 

The  tissue  shown  in  the  drawing  includes  the  middle  cere- 
bellar  peduncles  which  have  been  divided  for  the  removal  of 
the  cerebellum.  It  thus  forms  an  antero-posterior  section  of  the 
annular  protuberance,  or  pom,  at  its  middle  portion.  The 
anterior  rounded  part  corresponds  to  the  foot,  the  posterior 
slightly  flattened  part  to  the  floor  of  the  fourth  ventricle.  In 
the  foot  are  a  number  of  thick  fasciculi  of  fibers  cut  longi- 
tudinally, mixed  up  with  little  cells — the  pontine  nuclei.  These 
fibers  form  a  thick  bundle  on  each  side  which  are  cut  trans- 
versely: they  are  the  ponto-cerebellar  fibers  and  enter  into  the 
composition  of  the  middle  cerebellar  peduncles  and  participate 
in  the  accessory  motor  paths.  In  the  middle  and  a  little 
behind  these  are  two  large  transversely  cut  bundles  of  fibers— 
the  pyramidal  tracts,  of  which  the  left  is  degenerated. 

Behind  these,  in  the  posterior  part  of  the  pons,  there  are 
various  structures:  fibers  and  masses  of  gray  matter  more  or 
less  rich  in  cells  (nuclei  of  the  cranial  nerves).  The  principal 
of  the  structures  are  as  follows:  the  median  ribbon  of  Peil  on 
each  side  of  the  median  line ;  the  posterior  longitudinal  fasci- 
culus; the  acoustic  striae  and  the  arciform  fibers  in  the  white 
substances;  the  pontine  olive  also  called  the  superior  olive,  a 
little  mass  of  gray  matter  placed  at  the  anterior  part  of  the 
anterior  portion  of  the  pons.  It  only  shows  to  the  left  of  the 
median  line;  the  section  being  a  little  oblique  does  not  pass 
through  it  on  the  right  side. 

In  fine,  the  only  lesion  that  is  to  be  found  in  the  section  is 
the  degeneration  of  the  pyramidal  tract  of  the  left  side  following 
closely  upon  that  seen  in  the  last  section. 

Fig.  85  represents  a  section  of  the  medulla  at  its  middle 
part  where  it  passes  through  the  olivary  bodies,  flattened  layers 
of  gray  substance  having  an  undulating  arrangement  and  bend- 
ing so  as  to  make  a  kind  of  horse-shoe,  the  opening  in  which  is 
directed  toward  the  median  line,  and  a  little  posteriorly.  These 
bodies,  which  attract  immediate  attention,  facilitate  the  diag- 
nosis of  the  organ  and  approximately  indicate  the  height  at 
which  the  section  was  cut.  Between  the  olives  and  extending 
backward  almost  to  the  floor  of  the  fourth  ventricle  is  a  layer 
of  transversely  cut  fibers,  the  inter-olivary  layer  or  sensory  tract 
(median  tract  of  Reil).  A  little  to  the  outer  side  of  the  sensory 
tract  are  the  fibers  of  the  great  hypoglossal  nerve,  the  XII 

190 


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cranial  nerve,  which  arises  from  a  nucleus  situated  immediately 
below  the  floor  of  the  bulb,  near  the  middle  line,  to  pass  out 
a  little  in  front  and  outside  of  the  pyramidal  tract,  which 
makes  a  slight  projection  in  front  of  the  section  on  each  side  of 
the  median  line. 

At  the  inferior  angle  of  the  section  is  a  thick  layer  of  trans- 
versely cut  fibers:  the  restiform  body,  with,  at  its  internal  part, 
the  vestibular  nucleus  of  Deiters. 

Between  the  nucleus  of  Deiters  and  the  hypoglossal  nucleus 
there  is  an  isolated  bundle:  the  solitary  fasciculus,  a  sensory 
root  of  mixed  nerves,  notably  of  the  tenth  pair,  or  pneumo- 
gastrics,  of  which  the  posterior  nucleus,  nucleus  of  the  gray 
wing  may  be  seen  under  the  floor  of  the  fourth  ventricle,  imme- 
diately outside  of  the  nucleus  of  the  twelfth  nerve,  and  the 
anterior  nucleus,  or  ambiguous  nucleus  at  the  middle  of  the 
reticulated  structure  of  the  bulb.  Some  oblique  fibers  directed 
forward  and  outward  can  be  distinguished  between  the  two 
nuclei  of  the  tenth  nerve:  they  are  the  radicular  fibers  of  the 
pneumo gastric,  which  are  on  their  way  to  emerge  at  some  dis- 
tance outside  of  and  behind  the  swelling  of  the  olivary  body. 

Finally,  in  front  and  above  in  the  drawing  are  the  two  pyra- 
mids containing  the  pyramidal  tracts.  On  the  left  the  pyramid 
is  somewhat  diminished  in  size,  and  is  of  a  gray  color;  degen- 
eration of  the  pyramidal  tract  on  the  left  side,  following  upon 
those  described  above.  In  the  right  pyramid  there  is  a  fine 
band  of  gray  matter  bounded  anteriorly  and  internally  by  the 
pyramidal  tract,  which  should  not  be  mistaken  for  degenera- 
tion. It  is  a  special  gray  formation :  the  arciform  nucleus  of  the 
bulb,  in  which  the  cells  can  be  seen  with  a  higher  lens. 

The  three  sections  which  follow  are  of  the  spinal  cord  and 
have  as  common  characteristics  an  ovoid  shape,  central  gray 
matter  arranged  in  the  form  of  a  letter  H,  and  surrounding  white 
matter  almost  entirely  made  up  of  transversely  cut  fibers. 

As  representation  of  spinal-cord  structure,  the  cervical 
spinal  cord  (Fig.  86)  will  first  be  considered.  The  section  is 
divided  into  symmetrical  halves,  in  front  by  a  broad  and  deep 
fissure,  reaching  downward  to  the  transverse  branch  of  the  H, 
into  which  penetrate  the  meninges  and  the  vessels,  and  behind 
by  an  incomplete  fissure  continued  by  a  narrow  septum  of 
neuroglia. 

On  each  side  of  the  cord  the  gray  and  white  matter  are  clearly 
differentiated.  The  gray  matter  is  expanded  into  large  masses 
anteriorly,  and  contains  large  multipolar  nerve  cells  easily  visible 
under  a  low-power  lens :  the  radicular  cells.  The  posterior  horn 
is  slender  and  reaches  to  the  periphery  of  the  section  where  it 

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is  continued  into  the  posterior  nerve  root;  at  the  extremity  of 
these  horns  are  the  zones  of  Lissauer. 

The  two  halves  of  gray  matter  are  united  by  a  transverse 
branch,  the  gray  commissure,  in  the  middle  of  which  is  the 
central  canal,  lined  with  the  cuboidal  cells  of  the  ependyma. 
The  peculiar  shape  of  the  anterior  horn,  the  presence  of  a 
little  lateral  point  at  the  base  of  each  (lateral  horn),  together 
with  the  shape  and  large  size  of  the  section  enable  the  cervical 
cord  to  be  recognized. 

On  each  side  of  the  anterior  surface,  at  some  distance  outside 
of  the  deep  anterior  median  fissure,  there  is  a  slight  and  indis- 
tinct depression :  the  anterior  collateral  fissure,  through  which 
the  anterior  radicular  fibers — anterior  nerve  roots — pass  out. 
The  white  matter  is  thus  divided  into  three  columns:  anterior, 
lateral  and  posterior. 

The  posterior  columns  are  composed  entirely  of  posterior 
roots:  the  anterior  and  lateral  are  combined  under  the  name 
antero-lateral  columns,  and  include  all  the  remainder  of  the 
cord.  The  posterior  column  is  further  divided  into  two  por- 
tions, indistinctly  separated  in  sections  of  normal  tissue,  the 
differentiation  being  based  chiefly  upon  the  study  of  its  degen- 
eration: an  internal  fasciculus,  the  column  of  Goll  and  an  exter- 
nal fasciculus,  the  column  of  Burdach. 

In  the  antero-lateral  column,  in  addition  to  the  association 
fibers  that  connect  at  different  levels,  there  are  the  following: 

1.  On  each  side  of  the  anterior  median  fissure,  a  narrow  band 
corresponding  to  the  direct  pyramidal  tract. 

2.  In  the  remainder  of  the  antero-lateral  column  there  are  three 
important  fasciculi,  the  crossed  pyramidal  tract,  directly  against 
the  gray  matter,  the  direct  cerebellar  tract,  and  a  fasciculus  of 
Cowers  thrust  out  toward  the  periphery. 

The  cord  is  surrounded  by  a  layer  of  pia  mater  that  contains 
vessels  not  only  belonging  to  the  membrane  itself  but  also 
those  that  penetrate  into  the  substance  of  the  cord  to  form 
its  fibro-vascular  axes. 

Alongside  of  and  external  to  the  posterior  horn  of  gray 
matter,  on  the  right  side,  is  a  large  decolorized  zone  that  does 
not  appear  on  the  other  side.  It  is  a  degenerative  lesion  which 
evidently  involves  the  entire  crossed  pyramidal  tract,  limited 
solely  to  the  fibers  of  the  crossed  pyramidal  tract  and  showing 
its  topography.  In  the  other  half  of  the  cord  there  is  a  narrow 
pale  degenerated  zone  in  front  and  along  side  of  the  anterior 
median  fissure,  representing  the  left  direct  pyramidal  tract, 

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This  degeneration,  crossed  on  the  right  and  direct  on  the 
left,  is  in  accord  with  what  we  have  observed  at  higher  altitudes : 
peduncles,  pons  and  bulb.  It  enables  one  to  demonstrate  the 
decussation  of  the  fibers  of  the  pyramidal  tract  which  takes 
place  at  the  bulb,  a  few  fibers  remaining  in  the  spinal  cord  on 
the  homolateral  side  (direct  pyramidal  tract),  but  the  greater 
part  passing  to  the  other  side  (crossed  pyramidal  tract). 

Fig.  87  shows  a  section  of  the  dorsal  cord,  which  can  be 
recognized  by  its  relatively  small  size,  the  narrow  and  attenu- 
ated anterior  and  posterior  horns,  and  above  all  by  the  presence 
of  an  oval  mass  of  gray  matter:  the  column  of  Clark,  character- 
istic of  the  dorsal  cord,  on  the  internal  surface  of  the  posterior 
horn,  in  the  neighborhood  of  the  gray  commissure. 

The  same  degenerated  tracts  are  found  here  as  in  the  cervical 
cord;  to  the  left  in  the  anterior  column,  the  direct  pyramidal 
tract:  on  the  right,  in  the  lateral  column,  the  crossed  pyramidal 
tract,  the  shape  and  size  of  which  are  a  little  different  from 
those  seen  in  the  other  sections. 

Fig.  88  represents  a  section  of  the  lumbar  cord  in  its  middle 
part.  It  is  recognized  by  the  swollen  appearance  of  the  ante- 
rior horns  of  the  gray  matter,  rounded  and  a  little  projected 
externally,  by  the  absence  of  the  lateral  horn,  and  the  irregularly 
circular  shape  of  the  section 

There  is  no  longer  degeneration  of  the  left  anterior  column 
because  the  direct  pyramidal  tract  disappears  at  the  inferior 
part  of  the  dorsal  cord.  But  the  degeneration  in  the  lateral 
bundle  can  still  be  distinctly  seen  on  the  right  side  in  the  crossed 
pyramidal  tract. 

Resume. — Descending  degeneration  of  the  motor  nerves, 
affecting  the  pyramidal  tract  in  its  entire  length,  can  be  traced 
through  different  attitudes  of  the  cerebrospinal  axis.  It  is 
the  only  lesion  observed  in  the  sections.  The  case  was  one 
of  softening  in  the  motor  area  of  Rolando  in  the  left  cerebral 
hemisphere  with  descending  degeneration  of  the  pyramidal 
fibers,  which  in  the  cord  are  found  partly  on  the  left  side,  but 
in  greater  part  on  the  right  side,  because  of  the  decussation  of  the 
greater  part  of  the  pyramidal  tracts  in  the  medulla.  Thus  is 
explained  why  lesions  of  the  left  hemisphere  (region  of  Rolando) 
occasion  motor  symptoms  (hemiplegia)  of  the  right  side  of  the 
body. 

Resume. —  Hemiplegia  following  a  lesion  of  the  left  hemisphere. 

196 


TABES  DORSALIS. 

Diagnosis  of  the  Organ. — The  cervical  spinal  cord  can  be 
easily  recognized  by  its  oval  and  laterally  extended  shape,  the 
size  of  the  anterior  cornua,  their  quadrilateral  form  which 
depends  upon  the  presence  of  the  lateral  horn,  and  by  the 
depth  of  the  anterior  median  fissure. 

Diagnosis  of  the  Lesion.— That  which  at  once  strikes  the 
observer  is  the  small  size  of  the  posterior  horns  of  the  gray 
matter  which  are  atrophied,  though  not  degenerated  in  their 
entire  extent.  Areas  of  healthy  dark-colored  fibers  separate 
the  degenerated  pale  areas.  The  most  degenerated  portions 
on  each  side  form  a  hand  corresponding  to  the  external  part 
of  the  columns  of  Burdach.  This  little  tract  bifurcates  at 
its  postero-external  part  in  the  form  of  a  fork  whose  two  branches 
surround  an  almost  normal  zone,  the  external  band  of  Pierret. 
The  more  interior  part  of  the  posterior  column,  or  column  of 
Goll,  is  a  great  deal  less  degenerated  than  the  column  of  Bur- 
doch.  The  posterior  nerve  roots,  cut  transversely  or  longi- 
tudinally are  completely  degenerated.  Their  entrance  into  the 
cord,  the  zone  of  Lissauer,  is  equally  affected  and  appears 
bleached.  The  external  fasciculus  being  an  ascending  prolonga- 
tion of  the  posterior  nerve  roots,  having  penetrated  lower  down, 
the  lesion  passes  through  the  posterior  roots  in  their  intramed- 
ullary  as  in  their  extramedullary  course  (posterior  radiculitis) . 

The  zones  that  remain  intact  correspond  to  the  territory  of 
endogenous  fibers,  i.  e.,  to  those  fibers  that  have  their  cells  of 
origin  in  the  gray  substance  of  the  spinal  cord.  These  endo- 
genous zones  consist  at  first  of  a  kind  of  blackish  arch  situated 
immediately  behind  the  gray  commissure  and  extending  along 
the  posterior  horns — the  cornu-commissural  zone.  Between  the 
branches  of  the  fork  of  the  external  fasciculus  the  postero- 
external  field  is  found:  equally  a  territory  of  endogenous  fibers. 

Thus  the  distribution  of  the  endogenous  zones,  relatively 
simple  at  this  level  of  the  cervical  cord,  is  limited  to  the  cornu- 
commissural  zone  and  the  postero-external  fields. 

The  meninges  in  this  case  are  slightly  adherent  to  the  sclerosed 
zones  in  the  neighborhood  of  the  posterior  columns.  Other 
methods  of  staining — hematoxylon  and  eosin — would  show  a 
slight  infiltration  of  inflammatory  cells  in  the  meninges. 

Resume. — Tabes  dorsalis :  that  is  to  say,  of  degeneration  with 
sclerosis  of  the  nerve  roots  and  posterior  columns.  The  disease 
is  not  very  far  advanced,  as  the  degenerative  process  still  respects 
the  areas  of  the  endogenous  fibers. 

198 


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DISSEMINATED  SCLEROSIS. 

Diagnosis  of  the  Organ. — The  oval  shape  of  the  section,  in 
which,  in  spite  of  the  lesions,  the  gray  medullary  matter 
with  its  large  triangular  anterior  horn  and  slender  posterior 
horn,  reaching  to  the  periphery,  can  be  seen,  shows  it  to  be  a 
section  of  the  spinal  cord  at  the  altitude  of  the  cervical  en- 
largement. 

Diagnosis  of  the  Lesion. — One  is  struck  by  the  extent  and 
asymmetry  of  the  decolorized  zones  which  are  irregularly 
distributed  throughout  the  section.  These  pale  patches,  of 
which  three  are  situated  in  the  heart  of  the  antero-lateral  and 
posterior  columns,  are  shaped  like  wedges  forcing  themselves 
into  the  periphery  of  the  medullary  mass.  Under  a  higher 
magnification,  these  pale  areas  do  not  show  any  traces  of 
myeline  sheaths,  but  are  entirely  degenerated.  The  distribu- 
tion of  the  patches  is  devoid  of  system:  the  degenerated  zones 
do  not  correspond  with  either  tracts  of  nerve  fibers  (direct  or 
crossed  pyramidal)  or  even  with  the  gray  matter. 

The  patch  to  the  right,  for  example,  affects  the  entire  antero- 
lateral  column  except  its  anterior  angle  and  some  few  fibers  of 
the  direct  pyramidal.  It  also  equally  affects  the  gray  matter, 
but  seems  to  spare  the  nerve  cells  which  show  with  great  dis- 
tinctness as  brown  upon  the  white  background.  It  is  impossible 
any  longer  to  recognize  the  network  of  fibers  surrounding  the 
nerve  cells  in  the  anterior  horn.  Toward  the  inner  side  and 
in  front  the  patch  of  sclerosis  encroaches  a  little  at  the  bottom 
of  the  anterior  median  fissure,  upon  the  anterior  column  of  the 
opposite  side  of  the  cord.  There  is  no  invasion  of  the  poste- 
rior column  except  the  part  immediately  contiguous  to  the 
gray  commissure. 

It  is  an  old  lesion — neurogliar  sclerosis — of  which  the  details 
ought  to  be  shown  by  elective  stains.  If  the  lesion  were  fresh 
sclerotic  patches,  when  stained  by  the  Marchi  method  with 
osmic  acid,  fatty  vesicles  enclosed  in  the  interior  of  macro- 
phages  (compound  granular  cells  should  show). 

Resume.— The  presence  of  the  patches  of  sclerosed  degen- 
erated tissue,  without  system,  occurring  in  both  the  white  and 
gray  matter,  make  the  diagnosis  of  disseminated  sclerosis. 


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SYRINGOMYELIA. 

Diagnosis  of  the  Organ. — It  is  possible  to  recognize  the  cervi- 
cal cord  because  of  the  arrangement  of  the  gray  matter  in  the 
form  of  a  letter  H,  with  two  large  quadrilateral  anterior  horns, 
the  deep  anterior  median  fissure,  and  the  elongated  transverse 
diameter. 

Diagnosis  of  the  Lesion. — The  cord  flattened  antero-posteri- 
orly  is  more  elongated  than  normal.  In  its  center  is  a  long 
transverse  cavity  which  gives  the  section  a  pathognomonic 
appearance. 

1.  The  central  canal  has  an  asymmetrical  stretched  appear- 
ance, the  part  toward  the  right  side  being  the  most  disturbed. 
The  cavity  is  empty  and  its  walls  are  not  lined  with  the  cylin- 
drico-cubical  endothelium  of  the  ependymal  canal  which  so 
much  resembles  epithelium.     The  cavity  is  surrounded  by  a 
quite  thick  band  of  structureless  tissue  that  has  not  taken  the 
Weigert  stain  and  which  under  a  higher  magnification  presents 
a  finely  granular  or  a  vaguely  fibrillar  appearance.     It  is  a 
special  tissue,  the  neuroglia,  the  demonstration  of  which  requires 
special  staining  such  as  that  of  Lhermitte. 

The  condition  is  glioma  or  a  gliosis  of  the  spinal  cord,  of 
which  the  center  has  softened  and  given  origin  to  a  cavity. 
This  gliosis  has  very  precise  limits:  in  front,  the  anterior 
white  commissure  composed  of  horizontal  fibers,  behind  the 
posterior  columns,  laterally  the  internal  substance  of  the  gray 
matter  where  it  penetrates  a  little  into  the  posterior  and  some- 
times also  into  the  anterior  horn. 

In  the  clinic  this  condition  may  give  rise  to  muscular  atrophy. 

2.  Central  gliosis  of  the  lateral  columns,  with  degeneration 
of  the   two  crossed  pyramidal    tracts:    a    degeneration    that 
presents  itself  in  the  form  of  a  transversely  elongated  band 
following  the  flattening  of  the  cord  after  collapse  of  its  central 
cavity,  may  occur  as  an  accessory  lesion. 

Such  pyramidal  tract  degeneration  is  due  to  the  interruption 
of  the  fibers  at  a  point  above  liiat  at  which  the  section  has 
been  made,  by  a  cavity  analogous  to  but  more  extended  than 
that  which  we  have  been  studying. 

Resume. — The  transverse  slit,  the  gliosis  which  surrounds  it 
and  the  absence  of  an  ependymal  epithelium  lining  the  cavity 
permit  the  diagnosis  of  syringomyelia.  The  only  condition 
that  can  be  confused  with  it  is  hydromyelia  which  is  a  dilata- 
tion of  the  central  ependymal  canal  with  modified  but  recog- 
nizable ependyma,  and  without  neuroglia  new  formation. 

202 


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203 


ACUTE  ANTERIOR  POLIOMYELITIS. 

Diagnosis  of  the  Organ. — It  is  a  section  of  the  lumbar  cord 
as  can  easily  be  recognized  by  the  globular  shape  of  the  anterior 
horn  and  the  absence  of  a  lateral  horn. 

Diagnosis  of  the  Lesion. — Under  a  low-power  magnification  a 
number  of  distinct  small  dark  points  can  be  seen  in  the  gray 
matter  of  the  anterior  and  posterior  horns.  These  are  the  gan- 
glionic  nerve  cells.  In  the  white  matter  there  is  a  fine  stippling 
in  the  form  of  lines  radiating  from  the  periphery  to  the  gray 
matter. 

Under  a  higher  power  lens,  small  round  cells — embryonal 
cells  or  lymphocytes — can  be  seen  disseminated  irregularly,  or 
united  to  form  small  inflammatory  nodules  in  the  gray  matter. 
The  larger  of  these  are  not  centered  about  any  visible  element, 
but  the  smaller  can  be  seen  to  surround  vessels  or  more  or  less 
altered  ganglionic  nerve  cells.  This  infiltration,  particularly 
abundant  in  the  anterior  horn,  encroaches  a  little  upon  the 
base  of  the  posterior  also,  and  occurs  in  the  form  of  fine  lines 
in  the  vascular  connective-tissue  trabeculae  of  the  white  matter. 

The  nerve  cells  of  the  anterior  horn  (Fig.  92,  B)  show  atrophy 
which  explains  the  palsy  and  muscular  atrophy  observed  in  the 
clinic.  These  cells,  very  much  diminished  in  number,  are  not 
arranged  in  groups  as  in  the  normal  condition.  Some  still 
show  large  nuclei  with  nucleoli  and  protoplasmic  granules. 
But  the  greater  number  are  much  changed  through  the  dis- 
appearance of  their  protoplasmic  prolongations,  the  rounded 
shape  of  the  cell  bodies  and  the  excentric  position  of  the  nuclei 
which  may  be  strongly  colored  or  have  disappeared  through  frag- 
mentation of  the  protoplasm. 

Immediately  about  the  nerve  cells  the  lymphocytes  seem 
to  encroach  upon  the  protoplasm  and  even  to  penetrate  into 
the  cell  to  devour  it:  a  form  of  phagocytosis  called  neurono- 
phagia,  much  discussed. 

The  vessels,  apart  from  the  perivascular  infiltration,  the 
connective  tissue  and  the  meninges  show  nothing  in  particular. 

The  triangular  mass  of  cells  in  the  center  of  the  section  is 
a  proliferation  of  the  ependyma  (ependymitis). 

Resume. — It  is  an  acute  inflammatory  lesion  chiefly  affecting 
the  gray  matter  of  the  anterior  horns  of  the  lumbar  cord,  but 
extending  equally  into  the  white  matter  along  the  vascular 
connective  tissue  axes.  It  results  in  the  destruction  of  the 
motor  nerve  cells:  poliomyelitis  anterior  acute. 

204 


Anterior 
horn. 

Inflam- 
matory 
vessels. 


Strands  of 
inflam- 
matory 
cells. 


Disappearing  degenerated  nerve  cell 


Prolifera- 
tion of  the 
ependy- 
mal  cells. 


Normal 
nerve 
cell  of  the 
anterior 
horn. 
Degener- 
ated 
nerve  cell. 

Collec- 
tions of 
lympho- 
cytes. 

B 


Fig.  92. — Acute  anterior  poliomyelitis.     Section  of  the  lumbar  spinal 

cord. 


Stained  with  hematoxylon  and  eosin. 


From  a  young  soldier  dying  of  epidemic  acute  anterior  polio- 
myelitis with  bulbar  lesions. 

A. — Shows  numerous  infiltrations  in  the  anterior  and  posterior 
horns  of  the  gray  matter,  and  fine  lines  of  inflammatory  infiltration 
in  the  white  matter,  magnified  15  diameters. 

B. — Shows  the  progressive  disappearance  of  the  nerve  cells  of 
the  anterior  horn,  magnified  100  diameters. 

205 


PURULENT  LEPTOMENINGITIS. 

Diagnosis  of  the  Organ. — A  section  of  the  cerebral  cortex 
showing  a  characteristic  festooned  line  which  enables  the  organ 
to  be  recognized  as  brain.  The  size  of  the  convolutions  shows 
the  section  to  be  from  the  cerebrum,  as  those  of  the  cerebellum 
are  not  only  much  smaller  but  branched  in  an  arborescent 
fashion. 

Fig.  93  shows  one  of  the  fissures  or  sulci  separating  two  con- 
tiguous convolutions.  The  entire  depth  of  the  fissure  is  occu- 
pied by  a  dark-colored  band  representing  the  pia  matter,  in  this 
case  much  thicker  than  normal. 

Passing  through  the  gray  matter  of  the  cortex  from  the 
surface  downward,  it  is  possible  to  recognize  numerous  layers 
of  cells:  (i)  The  outer  molecular  layer,  composed  of  undiffer- 
entiated  round  or  oval  cells,  with  central  nuclei;  (2)  the  middle 
pyramidal  layer,  composed  of  triangular  cells,  with  numerous 
prolongations  (prolongations  of  Deiters)  and  a  basal  nucleus 
with  a  large  nucleolus;  (3)  large  pyramidal  cell  layer,  composed 
of  large  cells  (giant  cells  of  Betz)  and  polymorphous  cells. 

Diagnosis  of  the  Lesion. — The  pia  mater  forms  a  thick  mem- 
brane in  which  there  is  a  fine  meshwork  of  fibrin.  In  the  interior 
of  the  meshes  of  the  middle  layer  there  are  a  great  number  of 
larger  and  smaller  cells,  polymorphonuclears  and  large  and  small 
mononuclears,  betraying  an  acute  inflammatory  lesion. 

Their  protoplasm  stains  strongly  with  eosin  (acidophilic). 
Their  nuclei  stain  uniformly  (pycnosis).  In  a  word,  it  is  a 
purulent  exudate  which  covers  the  external  surface  of  the 
convolutions  and  penetrates  in  the  least  folds  of  the  cerebral 
fissure.  The  vessels  are  abundant,  dilated  and  congested. 

With  the  aid  of  a  special  selective  stain  (toluidin  blue,  Gram's 
etc.)  the  presence  of  the  causative  microorganism,  in  this 
case  the  pneumococcus,  can  be  demonstrated. 

In  a  section  stained  simply  with  hematoxylin  and  eosin  it  is 
difficult  to  see  the  changes  in  the  cortical  nerve  cells  (lesions 
of  atrophy,  which  show  blue  by  Nisl's  method  of  staining). 

Resume. — Acute  inflammation  of  the  pia  mater,  purulent 
leptomeningitis ,  of  which  it  is  difficult  to  find  the  cause.  The 
further  study  of  the  specimen  by  methods  of  staining  designed 
to  demonstrate  bacteria,  and  information  obtained  from  the 
autopsy  are  needed  to  complete  the  diagnosis,  and  permit  one 
to  say  as  here  that  it  was  caused  by  the  pneumococcus. 

206 


Meninges. 

Dilated 
vessel. 


Cortex. 

Molecular 
layer. 


Pia 

infiltrated 
with  pus. 


Invagina- 
tion  ot  pia 
mater  in- 
filtrated 
with  pus. 


Arteriole 
of  the  pia 
mater. 


Medium 
pyramidal 
cell  layer. 


Large 
pyramidal 
cell  layer. 


Fig.  93. — Purulent  cerebral  meningitis. 
Stained  with  hematoxylon  and  eosin.     Magnified  30  diameters. 

Purulent  leptomeningitis  in  an  old  man  aged  eighty  years. 
The  autopsy  showed  it  to  be  secondary  to  pneumonia  with  empyema. 
The  drawing  shows  a  cortical  cerebral  sulcus  into  which  the  pia 
mater,  infiltrated  with  pus  dips  down  between  the  convolutions. 


207 


EPIDEMIC  CEREBROSPINAL  MENINGITIS. 

Spinal  Meningitis. 

Diagnosis  of  the  Organ. — It  is  easy  to  recognize  a  section  of 
the  spinal  cord,  in  which  the  gray  matter  stands  out  distinctly 
upon  a  pale  background.  The  anterior  horn  of  gray  matter  is 
small,  the  posterior  slender  and  the  presence  of  Clark's  column 
shows  that  it  is  of  the  dorsal  cord. 

Diagnosis  of  the  Lesion. — The  cord  is  surrounded  by  a  dark- 
colored  sheath,  the  pia  mater  greatly  thickened. 

Even  with  a  low-power  lens  it  is  possible  to  see  a  fine  dark- 
colored  stippling,  very  dense  and  with  numerous  dilated  vessels, 
which  are  sufficient  to  make  the  diagnosis  of  meningitis. 

A  higher  power  magnification  (Fig.  94,  B)  shows  an  extensive 
infiltration  of  inflammatory  cells;  polymorphonuclears  and 
mononuclears  in  a  state  of  granular  and  fatty  change,  nuclei 
without  chromatic  details  forming  a  homogeneous  mass  deeply 
staining  with  the  hematoxylon  (pycnosis),  and  protoplasm  with 
fine  fatty  vacuoles.  A  little  further  advance  of  the  process, 
and  the  nuclei  disappear  and  the  cells  become  homogeneous 
masses.  Here  and  there  little  dark  granules  represent  frag- 
ments of  nuclei  or  of  cell  protoplasm  (cell  necrosis,  globules  of 
pus). 

The  inflammatory  cells  are  disseminated  without  order  and 
without  special  grouping  in  fine  meshes  of  fibrin,  similar  to 
those  seen  in  the  lung. 

In  the  remainder  of  the  section,  that  is  to  say,  in  the  spinal 
cord  itself,  nothing  further  abnormal  is  to  be  seen,  or  at  most 
only  fine  lines  of  cellular  infiltration  along  the  connective-tissue 
septae,  which  penetrate  from  the  periphery  toward  the  center 
as  radii. 

Resume — One  makes  the  diagnosis  of  purulent  spinal  men- 
ingitis, on  account  of  the  great  number  of  degenerating  poly- 
morphonuclears. Selective  bacterial  stains  (toluidin  blue  or 
Gram's  method)  should  reveal  the  presence  of  encapsulated 
diplococci — meningococci — sometimes  inclosed  in  the  interior  of 
the  mononuclear  cells. 

It  is  a  case  of  epidemic  cerebro spinal  meningitis. 


208 


Posterior 
nerve 
root. 

Meninges 

infiltrated 

with  pus. 


Posterior 

spinal 

artery. 

Posterior 
root. 


Degener- 
ating 
poly- 
morpho- 
nuclears. 


Posterior 
horn. 


Clarke's 
column. 

Anterior 

horn.     l::_..  •  • ,  ;      •  •  -   •"•":"  £^!!*!J^'4*^$,^J^1  Fibrinous 

network. 

B 

Fig.  94.— Cerebrospinal  meningitis. 

Stained  with  hematoxylon  and  eosin. 

Epidemic  cerebro spinal  meningitis  in  a  young  soldier  aged 
twenty-one  years. 

A. — Shows  the  dorsal  spinal  cord  with  the  posterior  meninges 
infiltrated  with  pus,  magnified  12  diameters. 

B.— Shows  a  part  of  the  meninges  with  polymorphonuclears  and 
mononuclears  in  a  state  of  degeneration. 


209 


PSAMMOMA. 

Calcified  Fibroma  of  the  Meninges. 

Upon  examining  the  section  under  a  low-power  magnification, 
the  same  characteristic  appearance  will  be  seen  everywhere, 
due  to  the  presence  of  a  multitude  of  small,  rounded,  trans- 
parent, refracting  bodies  of  variable  size,  separated  one  from 
another  by  a  tissue  which  constitutes  the  stroma  of  the  tumor. 
A  medium-power  magnification  enables  one  to  recognize  this 
variety  of  tumor  which  neither  resembles  any  other,  nor  any 
normal  tissue  of  the  body. 

In  studying  it  let  attention  be  paid  to  the  small  rounded 
bodies,  and  to  the  vascular  connective  tissue  between  them. 

I.  The  rounded  masses  are  calcareous  or  hyaline  and  of  a 
very  peculiar  appearance.     The  largest,  structureless,  without 
cells  or  nuclei,  are  formed  of  a  series  of  concentric  lamellae, 
and  show  at   the  center  or  periphery  bluish  patches  caused 
by  the  affinity  of  the  calcareous  matter  for    the   hematoxylon 
stain.     Connective-tissue  cells  gather  about  the  bodies.     Other 
smaller,  but  similar  bodies  are  without  calcification,   though 
equally  homogeneous  and  structureless:  hyaline. 

The  very  smallest  of  the  bodies  are  formed  of  concentrically 
arranged  connective-tissue  cells  compressed  like  the  coats  of 
an  onion. 

II.  The  connective- tissue  stroma  which  separates  the  bodies 
from  one  another  is  young  and  is  characterized  by  a  great 
number  of  fibroblasts  and  relatively  few  fibers.     The  appearance 
is  the  same  as  is  found  in  connective-tissue  tumors — fibroma  or 
sarcoma  (fibrosarcoma). 

The  vessels  of  the  tumor  are  not  abundant,  and  are  either  of 
the  adult  type  or  are  capillaries  with  a  simple  endothelial  wall. 

The  concentric  calcareous  or  hyaline  bodies  give  the  tissue 
of  the  tumor  a  certain  degree  of  friability,  which  explains  the 
rough  and  frayed  appearance  of  a  cut  surface. 

The  bodies  seem  to  be  formed  from  the  endothelial  lining 
of  the  vessels  whose  cells  proliferate  either  inside  or  outside, 
giving  rise  at  first  to  buds,  then  to  concentric  bodies,  and  then 
charge  themselves  with  calcareous  salts.  This  origin  can  be 
completely  verified  in  some  of  the  tumors. 

Hence  the  name  calcareous  fibroma  or  psammoma  given  to 
the  tumor. 


210 


Hyaline 
bodies. 


Calcified 
body. 


Fig.  95.— Psammoma. 

Stained  with  hematoxylon  and  eosin.     Magnified  80  diameters. 

A  tumor  oj  characteristic  appearance  and  sandy  consistence 
not  infrequently  observed  in  the  meninges  either  of  the  brain  or 
spinal  cord,  essentially  benign,  and  sometimes  first  discovered  at 
autopsy,  not  having,  as  in  this  case,  provoked  any  symptoms  during 
life.  It  is  easily  enucleable. 


211 


NORMAL  THYROID  BODY. 

Large,  fairly  regular  rounded  spaces,  filled  with  a  homogene- 
ous material  colored  red  with  eosin,  giving  the  appearance  of  a 
glandular  organ  formed  of  separate  acini  separated  by  a  con- 
nective-tissue stroma. 

Under  a  medium  magnification  each  of  the  acini  is  found  to 
be  limited  by  a  fine  bluish  stippling,  the  nuclei  of  epithelial 
cells  with  indistinct  protoplasm.  In  fragments  of  tissue  taken 
at  autopsy  it  is  difficult  to  distinguish  the  finer  histological 
details  (principal  cells  and  colloidal  cells).  Both  seem  to  be 
of  the  same  type  and  composed  of  granular  protoplasm  contain- 
ing in  the  center  a  deeply  colored  nucleus. 

The  content  of  the  acini  or  vesicles  is  formed  of  an  amorphous 
homogeneous  substance  called  colloid,  retracted  at  some  points 
in  the  form  of  vacuoles  (artefacts  of  fixation).  The  colloid 
substance,  ordinarily  red,  and  frankly  acidophilic,  at  other  times 
appears  purple  (amphophilic) ,  or  even  blue  (basophilic) ,  these 
diverse  tinctorial  affinities  corresponding  to  different  chemical 
states.  Sometimes  the  colloid  has  an  appearance  as  if  in  pali- 
sades, or  is  marked  by  numerous  parallel  fissures  (artefacts 
of  preparation). 

The  slight  variations  in  the  size  of  the  vesicles  is  due  to 
tangential  or  central  sectioning. 

Between  the  acini  is  a  connective  tissue,  fairly  dense  in  the 
adults,  containing  numerous  blood  and  lymph  vessels,  and 
masses  of  undifferentiated  round  cells:  masses  of  young  acini. 

The  characteristic  appearance  of  the  acini  with  their  colloidal 
contents,  and  the  absence  of  efferent  ducts  enables  one  at  once 
to  recognize  a  gland  of  internal  secretion:  the  thyroid.  The 
relative  equality  in  the  size  of  the  vesicles  and  the  slight  devel- 
opment of  the  connective  tissue  indicate  a  normal  thyroid  and 
exclude  all  thought  of  a  goiter. 

Differential  Diagnosis. — Certain  of  the  histological  appear- 
ances may  lead  to  confusion,  and  it  is  possible  to  mistake  the 
section  for: 

1.  Edematous  lung,  with  the  capillaries  between  the  alveoli 
dilated.     The  epithelial  cells  desquamated  into  the  edematous 
fluid  filling  the  alveoli  and  the  broncho-vascular  axes  should 
be  searched  for  throughout  the  section. 

2.  Cavernous  angioma  (of  the  liver,  for  example),  formed  of 
cavities  filled  with  blood.     Under  a  high-power  magnification 
the  red  corpuscles,  the  endothelial  cells  of  the  walls  and  the 
hepatic  tissue  in  the  immediate  vicinity  ought  be  found. 

212 


Connec- 
tive tissue 
strom  a. 


Small 

vesicle  cut 

tangen- 

tially. 


Solid  cell 
mass. 


Vessels. 


Artificial 
vacuole 
in  the 
colloid 
substance. 


Normal 
vesicle. 


Fig.  96. —  Normal  thyroid  body. 
Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

The  relatively  equal  size  o]  the  thyroid  acini  is  to  be  noticed. 
Note  also  the  occasional  presence  o]  solid  masses  o]  cells  which 
are  to  be  referred  either  to  young,  not  yet  fully  formed  acini,  or  to 
acini  in  a  condition  oj  retrogression. 


213 


GOITER  WITH   IRREGULAR  VESICLES. 

Colloid  Goiter. 

Diagnosis  of  the  Organ. — It  is  easy  to  recognize  the  thyroid 
body  through  the  characteristics  already  given.  But  that 
which  strikes  one  as  remarkable  and  may  make  him  hesitate 
as  to  the  nature  of  the  organ  is  the  astonishing  disproportion 
in  size  between  the  different  acini.  If  in  the  normal  condition 
the  acini  are  of  uniform  size,  here,  on  the  contrary,  they  are 
very  different,  some  being  enlarged  to  veritable  cysts,  even 
visible  to  the  naked  eye  (cystic  goiter).  The  more  these 
morphological  alterations  affect  the  acini,  the  more  their  struct- 
ure is  modified.  In  proportion  as  they  become  distended,  their 
epithelium  becomes  flattened — from  cuboidal  to  flat — so  great 
may  be  the  distention.  At  some  points  the  walls  seem  to 
give  way  so  that  neighboring  vesicles  become  confluent  and 
thus  the  cysts  are  formed. 

The  colloid  contents  of  the  acini  are  but  slightly  altered. 
They  are  a  little  paler  and  a  little  less  acidophilic  as  regards 
their  staining,  than  in  the  normal  section  that  preceded;  they 
are,  however,  a  little  more  fluid  and  the  palisade-like  striae 
are  less  distinct. 

Between  the  larger  cysts  are  masses  of  little  vesicles,  more 
or  less  normal  in  appearance,  of  which  a  certain  number  are 
shown  in  the  central  part  of  the  drawing.  Sometimes  the  acini 
are  rounded  or  polyhedral,  sometimes  drawn  out  and  narrowed 
by  reciprocal  pressure.  Finally,  here  and  there  are  rounded 
masses  of  cells,  without  any  central  cavity,  suggesting  the 
appearance  of  the  embryonal  thyroid. 

In  other  parts  of  the  section  there  are  occasional  areas  of 
hemorrhage,  in  which  red  blood  cells  infiltrate  into  the  thyroid 
acini.  There  are  both  old  and  fresh  hemorrhages,  the  last 
recognized  by  the  presence  of  crystals  of  hematoidin  and  the 
absence  of  fresh  blood  corpuscles. 

The  stroma  consists  of  loose  connective  tissue,  small  in 
amount  and  showing  a  tendency  to  sclerosis. 

Resume. — A  goiter  characterized  by  the  irregularity  of  the 
acini  and  the  presence  of  colloid  cysts :  a  tendency  to  interstitial 
hemorrhage,  whose  occurrence  corresponds  to  the  clinical 
periods  of  rapid  growth. 


214 


Hemor- 
rhagic 
focus. 


Medium 

colloid 

cyst. 


Normal 


Fig.  97.— Colloid  goiter. 

Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

Unilateral  colloid  goiter  of  the  size  of  a  mandarin  orange,  taken 
from  the  neck  of  an  old  woman,  at  autopsy.  Note  the  enormous 
disproportion  in  the  size  of  the  acini,  the  occasional  large  cysts 
and  the  occasional  interstitial  hemorrhages. 


215 


GOITER  WITH  SMALL  ACINI. 

Parenchymatous  Goiter. 

Diagnosis  of  the  Organ. — This  is  somewhat  difficult  to  make 
because  the  structure  of  the  gland  is  so  modified.  However, 
in  most  cases  it  is  easy  to  see  that  it  is  an  organ  of  the  glandular 
type  with  acini  and  without  excretory  ducts,  which  added  to 
the  fact  that  the  acini  contain  colloid  substance,  enables  the 
thyroid  to  be  recognized. 

Diagnosis  of  the  Lesion. — In  the  upper  part  of  the  drawing 
the  section  shows  a  large  number  of  little  vesicles  almost  entirely 
of  the  same  size,  the  greater  number  of  which  do  not  contain 
any  of  the  colloid  substance,  and  others  of  which  contain  very 
little.  In  other  parts  of  the  section  they  are  closely  pressed 
one  against  another.  Between  these  glandular  acini  are  dense 
cell  masses  or  cords  of  a  bluish  color,  and  without  a  central 
lumen  or  cavity,  which  recall  the  appearance  of  the  fetal  thy- 
roid, and  which  sometimes  lead  to  the  lesion  being  called  fetal 
goiter. 

In  the  lower  part  of  the  drawing  the  histological  appearance 
is  different.  The  acini  become  very  few  and  more  or  less 
widely  separated  from  one  another  by  interstitial  tissue  -which 
takes  on  a  considerable  development.  The  stroma,  very  palely 
stained,  sometimes  forms  extensive  areas,  the  structure  of 
which  can  only  be  made  out  with  a  higher  power  lens.  Some- 
times it  consists  of  a  fibrillar  connective  tissue,  with  rare  fixed 
cells,  sometimes,  on  the  contrary,  of  a  homogeneous  amorphous 
tissue  of  the  hyaline  type,  or  in  still  other  cases  of  a  field  of 
pale  rose  color,  suggesting  edematous  fluid. 

Some  of  the  destroyed  acini  seem  to  be  no  more  than  cells 
bunched  together  in  the  interior  of  the  stroma. 

Adult  vessels  and  capillaries  appear  in  the  substance  of  the 
stroma,  and  sometimes  there  are  foci  of  hemorrhage. 

Resume.— Goiter  with  tiny  vesicles  or  tiny  acini  as  con- 
trasted with  the  form  described  just  previously.  This  micro- 
scopic variety  corresponds  to  the  macroscopic  type  known  as 
parenchymatous  goiter.  In  this  case  the  hypertrophy  of  the 
gland  is  due  to  the  increase  in  the  number  and  not  to  increase 
in  the  size  of  the  acini. 


216 


Hyaline 

and 

edema- 

tous 

stroma. 


Fig.  98.— Parenchymatous  goiter.     (Goiter  with  small  acini.) 

Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

The  tissue  was  removed  at  autopsy  from  the  neck  cf  an  old 
woman.  In  the  upper  part  of  the  drawing  the  goiter  is  character- 
ized by  the  presence  of  a  large  number  of  small  acini  mostly  empty 
of  colloid;  in  the  lower  part  the  acini  are  dissociated  by  edema  and 
hyaline  degeneration  of  the  stroma. 


217 


THE  NORMAL  ADRENAL  BODY. 

A  histological  section  of  the  adrenal  or  suprarenal  body  made 
perpendicularly  to  the  transverse  axis,  and  presenting  to  the 
naked  eye  the  characteristic  elongated  appearance,  and  under 
slight  magnification  two  concentric  layers  of  different  staining 
intensity.  These  two  layers  correspond  to  the  cortex  and 
medulla  of  the  adrenal  body.  The  following  details  of  histo- 
logical structure  make  the  diagnosis  clear. 

A.  The  Cortical  Zone. — This  is  composed  of  three  layers, 
recognizable  under  a  low  power,  which  passing  from  the  surface 
to  the  center  are : 

1.  The  Zona  Glomerulosa. — This  is  the  most  superficial  layer, 
and  lies  immediately  beneath   the  connective-tissue  capsule. 
It  is  composed  of  cellular  masses,  scarcely  acini,  composed  of 
cells   with   dark  protoplasm   and   darker   nuclei.     This   zone, 
easily  enough  recognizable  in  man,  forms  a  dark  line  at  the 
periphery  of  the  section.     Its  cells  are  of  an  undifferentiated 
type,   that  is  to  say,   their  protoplasm  is  homogeneous  and 
scarcely  tinted  by  the  eosin. 

2.  The  Zona  Fasciculata,  which  forms  the  greater  part  of  the 
Fig.  99,  B,  is  formed  of  parallel  columns  of  cells  between  which 
the  capillary  vessels,  easily  recognized  by  the  presence  of  red 
blood  corpuscles,  are  in  intimate  contact  with  the  cells.     This 
layer  is  composed  essentially  to  spongiocytes,  or  cells  in  the 
clear  protoplasm   of   which   is   an   extremely  fine   meshwork. 
This  appearance  is  caused  by  the  fact  that  the  cells  are  filled 
with  fat   (neutral  fat  or  lipoid)   dissolved  out  by  the  usual 
histological  reagents,  with  the  resulting  pale  and  reticulated 
appearance. 

At  the  bottom  of  the  drawing  there  are  some  cells  of  undiffer- 
entiated type  with  dark  granular  protoplasm. 

3.  The  Zona  Reticularis. — Here  the  spongiocytes  completely 
disappear  and  the  cells  have  an  undifferentiated  appearance, 
and  granular  protoplasm;    they  form  an  extensive  network,  in 
the  meshes  of  which  are  numerous  capillaries.     Here  and  there 
are  a  few  cells  containing  granular  pigment.     The  zona  reticu- 
laris  is  a  particularly  vascular  layer. 

The  three  layers  of  cells  represent  different  stages  in  the 
development  of  the  same  cell,  whence  the  variability  in  the 
thickness  of  the  layers  in  different  parts  of  the  section,  accord- 
ing as  the  gland  is  in  a  state  of  activity  or  repose. 

218 


Fascicular 

layer. 

Glomeru- 

lar  layer. 

Capsule. 


B 

Capsule. 


Glomeru- 
lar  layer. 


Fascicular 

layer  with 

spongio- 

cytes. 


Undiffer- 
entiated  " 
cells. 


Capillary.    HMtMf^^BftlyiMggg^p 
Fig.  99.— Normal  adrenal  body. 

Stained  with  hemato^ylon  and  eosin. 

A. —  Transverse  section  of  the  entire  adrenal  gland  magnified  15 
diameters.  The  medullary  substance  occupies  the  center,  the  corti- 
cal substance  being  seen  above  and  below. 

R.—Glomerular  and  fasciculate  layers  seen  under  a  magnifica- 
tion of  200  diameters.  Above  is  the  capsule  of  the  organ;  below 
the  drawing  continues  with  Fig.  100,  C. 


219 


B.  The  Medullary  Zone. — This,  forming  the  central  part  of  the 
organ,  differs  from  the  preceding  in  its  appearance  and  by 
staining  a  deep  blue-violet  color  in  sections  stained  with  hema- 
toxylon  and  eosin.  It  consists  of  an  extensive  epithelial  net- 
work in  which  the  elements  are  separated  by  capillary  blood- 
vessels. It  is  broader  than  the  zona  reticularis  with  which  it 
is  continuous  without  distinct  separations.  The  cells  have  a 
dark  granular  protoplasm  that  takes  the  hematoxylon  strongly : 
chromaffine  cells — so-called  because  they  are  distinctly  browned 
by  salts  of  chromic  acid.  The  center  of  the  medulla  contains 
numerous  vessels,  of  which  the  central  veins  are  large  and  have 
thick  walls. 

Lastly  it  must  be  pointed  out  that  the  medullary  substance 
contains  rare  and  disseminated  lymphoid  collections. 

The  stroma  of  the  gland  is  formed  of  fine  collagenous  fibrillae 
and  of  young  connective-tissue  cells,  the  former  rare  except  at 
the  periphery  of  the  organ  where  they  are  condensed  to  form 
its  capsule. 

Here  and  there  at  the  periphery  of  the  section,  but  at  points 
not  shown  in  the  drawing,  are  small  cellular  masses  composed 
of  spongiocytes  or  undifferentiated  cells  well  isolated  from  the 
remainder  of  the  gland  by  surrounding  connective  tissue. 
Such  epithelial  islands  occur  in  the  greater  number  of  adrenal 
glands,  and  when  the  number  is  not  excessive  have  no  patho- 
logical signification. 

In  the  periglandular  connective  tissue  it  is  always  possible 
to  find  small  groups  of  cells  deeply  stained  with  hematoxylon, 
and  of  the  nervous  type.  These  are  ganglionic  nerve  cells 
belonging  to  the  sympathetic  nervous  system. 

Resume. — The  histological  appearance  of  the  suprarenal 
gland  with  its  differentiated  cell  layers  and  the  absence  of  any 
ducts  is  characteristic  and  easy  to  differentiate  from  other 
blood  vascular  glands. 


220 


Capillary. 


Pigmented 
cells. 


Medulla: 

Chromaf- 
fine  cells. 


Capillary. 


Fig.  100. — Normal  adrenal  gland. 
Stained  with  hematoxylon  and  eosin.     Magnified  200  diameters. 

C.—  The  zona  reticularis  below  the  zona  fasciculata  shown  in 
the  preceding  drawing,  with  its  cells  in  irregular  anastomosing 
columns.  Some  of  the  cells  have  a  finely  granular  protoplasm, 
others  contain  pigmentary  granules. 

D. — The  medullary  substance.  It  consists  of  columns  of  large 
cells  whose  protoplasm  contains  granules  of  adrenalin.  These 
granules  turn  brown  upon  the  application  of  salts  of  chromium 
and  are  therefore  called  chromaffine  cells. 


221 


HYPERPLASTIC  ADRENAL. 

Diagnosis  of  the  Organ. — The  section  passes  through  all 
three  layers  of  the  adrenal.  Above,  beneath  the  connective- 
tissue  capsule,  the  glomerular  layer  is  scarcely  visible;  in  the 
center  is  the  zona  fasciculata,  below  this  is  the  zona  radicu- 
laris,  with  its  undifferentiated  cells,  and  at  the  bottom  is  the 
medullary  portion. 

Diagnosis  of  the  Lesion. — One  is  at  once  struck  by  the  great 
thickness  of  the  cortex,  which  is  almost  entirely  formed  of  the 
spongiocytes. 

Under  a  higher  power  lens  it  is  possible  to  recognize  the 
vacuolar  or  reticular  character  of  the  cells  as  in  the  normal 
adrenal,  but  the  nuclei  are  larger  and  sometimes  in  a  state  of 
division. 

Toward  the  right  hand  in  the  drawing,  the  arrangement  of 
the  fasciculi  has  the  normal  appearance;  the  cells  are  arranged 
in  long  parallel  columns  in  a  radiating  manner.  To  the  left, 
the  cellular  tubes  have  lost  all  regularity  of  direction,  some- 
times paralleling  the  surface  of  the  organ,  and  tending  to  arrange 
themselves  in  a  concentric  fashion  (adenomatous  hyperplasia). 
The  zona  reticularis,  at  the  right  inferior  portion  of  the  draw- 
ing, is  formed  of  undifferentiated  cells  in  short  columns.  Finally 
here  and  there  one  sees  some  pigment  cells. 

On  the  exterior  of  the  capsule,  at  points  not  shown  here, 
are  some  large  oval  masses  formed  of  spongiocytes. 

The  medulla,  which  is  partly  shown  in  the  lower  part  of  the 
drawing,  does  not  show  anything  abnormal. 

The  connective-tissue  stroma  appears  to  be  a  little  better 
developed  than  normal.  One  can  see  very  distinctly  the  thin 
connective- tissue  separations  between  the  columns  of  cells. 
So  far  as  the  capillaries  are  concerned,  especially  in  the  fas- 
ciculus, they  are  scarcely  visible,  being  compressed  between 
the  hypertrophied  columns  of  cells. 

Resume. — The  usual  histological  picture  is  modified  by  the 
great  thickness  of  the  cortex,  especially  in  the  zona  fasciculata 
in  which  the  spongiocytes  are  greatly  augmented  in  number 
and  in  size.  This  appearance  betrays  a  condition  of  hyper- 
plasia and. corresponds- anatomically  with  general  enlargement 
of  the  gland,  which  instead  of  weighing  4  to  6  grams  may  reach 
10  grams.  From  the  point  of  view  of  physiology  it  signifies 
excessive  function.  It  is  found  in  cases  of  Bright's  disease  and 
arteriosclerosis. 

222 


Undiffer- 

entiated 

cells. 


Connec- 
tive tissue 
capsule. 
Zona 
glomeru- 
losa. 


Undiffer- 

entiated 

cells. 

Capillaries. 


Zona. 

reticu- 

laris. 


Fig.  101. — Hyperplastic  adrenal  gland. 

Stained  with  hematoxylon  and  eosin.     Magnified  100  diameters. 

The  cortical  area  is  greatly  thickened,  especially  in  the  zona 
Jasciculata,  which  is  almost  entirely  composed  of  spongiocytes. 
Toward  the  right  of  the  figure  the  columns  of  cells  are  regularly 
arranged  and  parallel;  toward  the  left  they  are  confused,  and  show 
the  beginning  of  an  adenomatous  transformation. 


223 


HYPOPLASTIC  ADRENAL  BODY. 

Diagnosis  of  the  Organ. — The  adrenal  body  is  easily  recog- 
nized through  its  division  into  two  layers,  the  cortex  and  the 
medulla,  the  former  with  its  three  portions. 

Diagnosis  of  the  Lesion. — One  is  immediately  struck  by 
the  diminished  thickness  of  the  cortical  portion.  Comparing 
this  drawing  with  the  preceding,  it  is  found  that  the  thickness 
of  the  cortex  is  diminished  by  about  one-half. 

1.  The  glomerular  layer:     This  is  scarcely  visible,  but  one 
should  not  draw  conclusions  from  this  alone. 

2.  The  fascicular  layer:    This  shows  the  cells  well  arranged 
in  long  columns,  but  they  have  almost  lost  their  spongiocytic 
aspect;     scarcely  a  trace  of  the  vacuoles  being  seen  in  their 
protoplasm.     The    cells   are    small,    retracted   and   shrunken. 
In  some  of  them  the  nuclei  show  no  chromatic  structural  details 
and  have  become  pycnotic. 

At  occasional  points,  as  in  the  central  and  upper  parts  of  the 
drawing,  there  are  oval  areas  with  ill-defined  limits,  which  form 
pale  patches.  These  have  an  adenomatous  aspect,  and  are 
composed  of  less  differentiated  cells  than  those  we  have  been 
describing,  but  without  vacuolar  structure  as  in  the  normal 
spongiocytes. 

In  addition  to  the  cellular  alterations  a  slight  sclerosis  dissoci- 
ates the  cell  columns;  some  fine  connective-tissue  bands  isolate 
the  cells  from  one  another. 

3.  The  reticular  layer:     This  also   contains   retracted  cells 
poor  in  pigment,  but  whose  lesional  appearance  is  less  distinct 
than  in  the  fascicular  layer. 

In  regard  to  the  lesions  of  the  medulla,  they  are  of  slight 
importance. 

Resume. — The  histological  picture  is  the  reverse  of  that 
shown  in  the  last  specimen.  It  is  hypoplasia  of  the  adrenal 
generalized  throughout  the  entire  gland,  and  characterized  by 
the  absence  of  the  spongiocytes  and  the  return  of  the  cells  to 
the  undifferentiated  condition,  and  by  the  slight  sclerosis  that 
dissociates  the  cellular  elements.  This  hypoplasia  corresponds 
anatomically  to  a  diminution  in  the  size  of  the  gland,  which 
may  not  weigh  more  than  2  or  3  grams,  and  physiologically  to 
a  condition  of  hypofunctionation. 

It  is  seen  in  infectious  diseases  and  in  the  cachexias  of  cancer 
and  tuberculosis. 


224 


Vessels. 


Undiffer- 

entiated 

cells. 


Medul-f 
lary  cells.  \ 


Fig.  102. — Hypoplastic  adrenal  gland. 


Connec- 
tive  tissue 
I  capsule. 


Medulla 
Vessels. 


Stained  with  hematoxylon  and  eosin.     Magnified  500  diameters. 

The  connective-tissue  capsule  of  the  gland  is  thickened,  and  fine 
strands  descend  from  it  between  the  cellular  elements  which  they 
separate  (sclerosis).  The  cells  of  the  zona  fasciculata  have  lost 
the  spongiocytic  appearance,  and  are  smaller  and  darker  in  appear- 
ance: undijferentiated  cells. 


225 


NORMAL  HYPOPHYSIS  CEREBRI. 

A  microscopic  section  passing  through  the  hypophysis  close 
to  the  center  of  the  organ,  in  an  antero-posterior  direction  and 
having  a  very  peculiar  and  characteristic  appearance. 

When  examined  under  a  low-power  lens  (Fig.  103,  A),  the 
section  divides  itself  into  two  distinctly  limited  portions:  one, 
the  larger,  is  red-violet  and  rounded,  and  forms  nearly  the  whole 
of  the  section;  the  other  pale  rose-red,  scarcely  colored,  ovoid 
and  very  small.  One  of  the  poles  of  this  latter  is  partly  included 
in  a  recess  in  one  edge  of  the  former. 

Such  a  histological  appearance  is  truly  unique  and  at  once 
permits  the  assumption,  even  without  microscopical  examina- 
tion, that  we  have  to  do  with  a  section  of  the  hypophysis. 

The  hypophysis  is  then  composed  of  two  lobes,  the  one  a 
great  deal  larger  than  the  other  and  stained  blue-violet,  the 
glandular  or  anterior  lobe;  the  other  much  smaller,  and  stained 
rose-red,  the  posterior  or  nervous  lobe.  These  lobes  form  in  a 
certain  fashion  two  kinds  of  glands  pressed  together,  of  which 
the  origin  and  function  are  different.  Between  them  is  a 
connecting  portion,  the  intermediate  lobe. 

Under  a  higher  power  the  histological  details  of  the  different 
portions  can  be  studied. 

I.  The  Glandular  Lobe  (Fig.  103,  B). — This  is  formed  of  a 
series  of  cellular  elements  grouped  in  different  ways.  Some- 
times the  cells  form  little  masses  separated  from  one  another 
by  the  connective  tissue  and  vessels  of  the  gland;  sometimes 
and  more  rarely,  the  arrangement  takes  the  form  of  acini  and 
recalls  more  clearly  a  glandular  structure  (Fig.  103,  C).  The 
columns  or  masses  include  two  types  of  glandular  cells;  some 
have  a  clear  protoplasm  scarcely  stained,  so  that  it  is  only  the 
nucleus  that  indicates  the  presence  of  the  cell — chromophobic 
cells — others  have  protoplasm  that  stains  with  avidity  and  is 
finely  granular — chromophilic  cells. 

Among  the  latter  the  greater  number  stain  violet  (hema- 
toxylon),  and  are  called  basophilic;  the  others,  less  numerous, 
take  the  eosin  and  are  called  eosinophilic.  It  is  probable  that 
these  different  staining  reactions  of  the  granules  of  the  proto- 
plasm express  different  functional  conditions  of  the  cells.  It 
is,  however,  important  to  remember  that  in  the  normal  hypoph- 
ysis the  chromophobic  and  chromophylic  cells  occur  in 
about  equal  numbers  and  that  the  basophiles  are  less  numerous 
than  the  eosinophiles. 

226 


Nervous 
lobule. 


Capillary. 

Chromo- 
philic 


Chromo- 


cells. 


Capillary. 


Fig.  103. — Normal  hypophysis. 


A. —  Vertical  section  of  the  entire  organ  showing  its  three  lobes 
magnified  5  diameters, 

B. — Section  of  the  glandular  lobe  showing  the  different  types  of 
cells,  magnified  250  diameters. 

C.— Another  section  of  the  glandular  lobe  showing  two  acini 
filled  with  colloid. 

227 


In  the  acinous  formations  (Fig.  103,  C)  the  cells,  chiefly 
chromophylic,  line  small  cavities  in  which  a  colloid  substance 
exactly  comparable  to  that  of  the  thyroid  body  is  found.  Such 
acinous  formations  are  not  common,  however,  in  the  normal 
hypophysis. 

Between  the  different  cellular  components  is  a  fine  connective 
tissue  in  slender  fasciculi,  forming  the  stroma  of  the  gland. 
Numerous  capillary  vessels  are  in  intimate  contact  with  the 
cells.  One  sees  in  this  the  chief  characteristic  of  the  glands 
of  internal  secretion,  which  together  with  the  absence  of  ducts, 
easily  enables  the  diagnosis  to  be  made. 

II.  The  Nervous  Lobe. — This  presents  an  individual  structure 
that  in   no   way   resembles   a   parenchymatous   gland.     It   is 
formed  (Fig.   104,  D)  of  fine  collagenous  fibers  and  a  great 
number   of   neuroglia  fibrillae,   impossible   to   differentiate   by 
the  ordinary  methods  of  staining,  but  made  very  distinct  by 
the  special  and  specific  method  of  Lhermite.     In  the  depths 
of  this  fibrillar  stroma  are  numerous  nuclei,  and  finally,  here 
and  there  some  masses  of  pigmented  cells  the  origin  and  nature 
of  which  are  badly  known. 

III.  The  Intermediate  Lobe. — This  includes  a  series  of  cystic 
formations  of  very  varied  number.     They  are  acini  lined  by 
cubical  cells  filled  with  a  colloid  material,  sometimes  retracted 
and  fissured,  sometimes  colored  rose-red  by  the  eosin,  sometimes 
bluish  by  the  hematoxylon,  and  whose  morphological  appear- 
ances recall  the  vesicles  of  the  thyroid  body.     Between  the 
cysts  are  cells  of  the  glandular  type  of  the  anterior  lobe. 

Resume. — The  structure  of  the  hypophysis  is  sufficiently 
characteristic  for  its  tissue  to  be  easily  recognized  in  a  micro- 
scopic section.  That  which  is  most  difficult  is  to  appreciate  its 
normal  or  abnormal  condition. 

A  large  number  of  chromophile  as  opposed  to  the  chromo- 
phobe  cells,  frequent  acinous  formation  and  a  quantity  of  the 
colloid  substance,  added  to  the  increase  in  the  size  of  the  organ, 
suggest  a  gland  in  a  state  of  hypersecretion:  glandular  hyper- 
plasia. 

Opposed  characters  indicate  the  opposed  condition :  glandular 
hypoplasia. 


228 


Pigment- 
ary cells. 


Capillary. 


Nervous 
lobe. 


Fig.  104. — Normal  hypophysis. 

D. —  The  nervous  lobe,  magnified  200  diameters,  showing  its 
fibers  of  collagen  and  neuroglia  and  nervous  cells. 

E.—The  intermediate  lobe,  magnified  100  diameters,  with  its 
colloid  cysts  and  glandular  cells.  Below  a  fragment  of  the  nervous 
lobe. 


229 


SCLEROSIS  OF  THE  THYMUS. 

Diagnosis  of  the  Organ. — Examination  of  the  section  with  a 
low  .power  lens  shows  a  dense  tissue  divided  into  lobules  by  broad 
bands  of  connective  tissue  that  support  the  bloodvessels  (Fig. 
105,  A). 

With  a  medium  power  magnification  (Fig.  105,  B),  the  lobules 
are  found  to  resemble  the  lymphoid  organs,  the  spleen,  the 
tonsils  and  the  lymph  nodes,  being  composed  of  a  reticulum  in 
the  meshes  of  which  are  an  infinite  number  of  lymphocytes. 
At  certain  points  the  reticulum  can  be  seen  to  be  composed 
of  fibrillary  prolongations  anastomosing  among  themselves. 

The  lymphocytes  are.  small  cells  in  which  it  is  often  impossible 
to  distinguish  more  than  a  nucleus  surrounded  by  a  thin  coronet 
of  scarcely  visible  protoplasm.  There  are,  however,  occasional 
mononuclear  cells  with  abundant  pale  red  protoplasm. 

But  that  which  enables  the  organ  to  be  immediately  recog- 
nized is  the  presence  of  numerous  small  pale  masses  composed 
of  flattened  cells  arranged  one  upon  another  like  the  skins  of 
an  onion,  vaguely  recalling  the  pearly  bodies  of  the  squamous- 
cell  carcinoma,  known  as  the  corpuscles  of  Hassal,  and  charac- 
teristic of  the  thymus. 

Diagnosis  of  the  Lesion. — The  thymus  under  examination 
differs  from  the  normal  by  the  presence  of  broad  and  dense 
connective-tissue  trabeculae  that  send  fine  divisions  into  the 
interior  of  the  lobes. 

Resume. — It  is  a  chronic  inflammation  of  the  thymus  or  a 
chronic  sclerotic  thymitis,  characterized  by: 

1.  Excess  of  the  connective  tissue. 

2.  Architectural  transformation  which  no  longer  permits  the 
differentiation    of    the   lymphoid    elements   into   cortical   and 
medullary  zones. 


230 


Sclerosed  tissue 


B 

Sclerosed 

corpuscle 

of  Hassal. 


Sclerosed 
band. 


Lymphoid 
tissue. 


Lymphatic  tissue. 


Vessels. 


Vessels. 
Corpus- 
cles of 
Hassal. 


Lymphoid 
tissue. 


Vessels. 


Capillar- 
ies. 


Fig.  105. — Sclerosed  thymus  gland. 
Stained  with  hematoxylon  and  eosin. 

Portion  of  a  large,  firm,  sclerosed  thymus  gland  taken  at  autopsy 
from  an  infant. 

A. — Entire  section  magnified  5  diameters. 

R.—A  portion  of  the  same,  magnified  150  diameters,  showing  the 
corpuscles  of  Hassal  and  the  sclerotic  bands. 


231 


NORMAL  FIBROBLASTIC  CONNECTIVE  TISSUE. 

In  this  section  we  will  consider  the  different  stages  in  the 
development  of  normal  and  pathological  connective  tissue. 

Drawing  A  represents  an  embryonal  connective  tissue,  essen- 
tially composed  of  cells,  the  fibroblasts,  distinctly  visible  but  not 
distinctly  differentiated.  They  have  abundant  protoplasm  and 
pale  nuclei  relatively  rich  in  chromatin,  which  at  certain  points 
may  show  a  tendency  to  lobulation  which  is  assumed  to  be  an 
indication  of  activity.  Between  these  cells,  arranged  in  parallel 
fashion,  are  opaque,  undulating,  striated  bands  of  variable 
size,  composed  of  delicate  nbrillse  of  collagen. 

At  the  left-hand  lower  corner  of  the  drawing  is  shown  a 
mononuclear  cell,  derived  either  from  the  blood,  or  from  the 
fibroblasts  through  metaplasia. 

Such  a  purely  fibroblastic  appearance  is  typical  of  the  embry- 
onal connective  tissues,  in  which  there  is  relatively  little  collagen. 

Similar  poverty  of  collagen  fibers  is  also  observed  in  certain 
malignant  tumors  of  connective- tissue  origin,  the  fibrosarcoma 
or  spindle-cell  sarcomas.  In  them,  however,  are  atypical 
cellular  and  nuclear  formations  not  found  in  the  normal  embry- 
onal connective  tissue. 

Drawing  B  shows  a  more  highly  developed  connective  tissue. 
The  fibroblastic  cells  have  become  flattened,  are  without  envel- 
opes, and  mold  themselves  to  the  spaces  between  the  collagen 
fibers.  The  nuclei  are  a  great  deal  darker,  the  mass  of  chroma- 
tin  being  condensed.  The  thickness  of  the  collagen  fibers  has 
greatly  augmented. 

The  origin  of  the  collagen  fibers  is  disputed.  It  is,  however, 
admitted  that  the  fundamental  amorphous  substance  that  will 
later  give  origin  to  the  collagen  is  a  part  of  the  primitive  con- 
nective-tissue cell,  which,  through  differentiation  may  give 
origin  to  either  collagen  or  elastic  fibers. 

In  Drawing  C  the  development  of  the  connective  tissue  has 
reached  an  adult  stage.  The  nuclei  and  bodies  of  the  fibro- 
blastic cells  are  reduced  to  a  sinuous  line  of  chromatin.  The 
collagen  fibers  have  become  much  larger  and  more  prominent, 
and  show  marked  undulation.  The  fibroblasts  seem  to  have 
been  smothered  by  the  collagen. 


232 


Nucleus 

of  a 

fibroblast. 


Fibro- 
blasts. 


Mononu- 

clear  cell. 

Collogen 

fiber. 

Nucleus 
of  fibro- 
blast. 
Collogen 
fiber. 

Interstice 

Fibro- 
blast. 

Nucleus 
of  a  fibro- 
blast 
greatly 
flattened. 


Nucleus. 

Collagen 
fiber. 


Fig.  106. — Normal  fibroblastic  tissue. 
Stained  with  hematoxylon  and  eosin.     Magnified  1500  diameters. 

A. — Connective  tissue  from  an  embryo,  showing  numerous  cells 
and  few  collagen  fibers. 

B.— Embryonal  connective  tissue  in  a  stage  of  further  develop- 
ment, showing  equality  in  the  proportion  of  cells  and  fibers. 

C. — Adult   connective   tissue.    It    contains    only   rare   nuclei 
smothered  in  the  collagenous  proliferation. 

233 


FIBROSARCOMA. 

Spindle-cell  Sarcoma. 

Dense  tissue,  in  which  the  cells  are  arranged  in  whorls  about 
the  vasculo-connective-tissue  axes  and  occasional  red-colored 
patches  betray  the  presence  of  small  hemorrhages.  This  is  all 
that  can  be  learned,  under  a  low  power,  from  the  topographical 
study  of  a  histological  section  taken  from  a  fibrosarcoma. 
The  appearance  under  a  higher  power  lens  is  shown  in  Fig.  107. 
In  the  center  of  the  drawing  is  a  section  of  a  capillary  whose  walls 
are  partly  formed  of  elongated  cells  with  fusiform  nuclei.  But 
these  cannot  be  found  on  the  right-hand  side  of  the  right-hand 
limb  of  the  capillary,  where  the  cells  of  the  tumor  seem  to  form 
the  actual  wall  of  the  vessel.  The  capillary  contains  a  few 
white  mononuclear  and  polymorphonuclear  leukocytes. 

The  greater  portion  of  the  section  is  composed  of  cells  with 
elongated  bodies  pointed  at  the  ends — young  fibroblasts  of  the 
connective  tissue — arranged  side  by  side  to  form  parallel 
fasciculi  of  cells  cut  transversely  which  gives  them  a  rounded 
appearance  with  central  or  peripheral  nuclei. 

The  vegetating  nuclei,  sometimes  constricted  at  the  center, 
like  an  hour-glass,  and  the  arrangement  of  the  chromatin  in 
equatorial  plates,  denote  a  great  reproductive  activity. 

A  tissue  presenting  a  uniform  structure  of  this  kind  is  in 
all  probability  a  tumor  of  the  connective  tissue.  But  the 
diagnosis  should  always  be  confirmed  by  information  received 
from  the  clinic  or  autopsy. 

Resume. — A  tumor  of  the  connective  tissue  composed  of  fibro- 
blasts: a  fibrosarcoma  or  spindle-cell  sarcoma.  It  is  regarded 
as  a  sarcoma,  that  is  to  say,  a  malignant  tumor,  rather  than  as 
a  fibroma,  which  is  a  benign  tumor  of  the  connective  tissue : 

I.  Because  it  is  extremely  rich  in  atypical  cells  with  mon- 
strous nuclei  and  karyokinetic  figures  which  indicate  its  tendency 
to  malignant  development. 

II.  Because  it  contains  numerous  newly  formed  vessels  whose 
walls  appear  to  be  cut  into  the  substance  of  the  tumor. 


234 


Mitosis. 


Fibro- 
blasts  cut 
trans- 
versely. 


Monstrous 
nuclei 


Fig.  107. — Fibrosarcoma. 


Fibro- 
blasts  cut 
longitu- 
dinally 


Capillary 
with  poly- 
morpho- 
nuclear 
cells. 


Mons- 
trous 
nuclei. 


Stained  with  hematoxylon  and  eosin.     Magnified  225  diameters. 

A  fibrosarcoma  of  the  nose,  not  yet  having  given  rise  to  metastasis 
at  the  time  it  was  removed  at  operation.  Note  the  imper/ect  char- 
acter of  the  central  capillary  and  the  numerous  cellular  mon- 
strosities. The  histological  structure  of  the  fibrosarcoma  explains 
its  anatomical  characteristics;  its  softness,  its  vascularity,  and 
its  tendency  to  hemorrhage.  Certain  inflammatory  processes  may 
afford  histological  pictures  very  similar  to  this,  but  the  uniformity 
of  the  structure  seen  here  ought  to  make  us  incline  toward  the 
diagnosis  of  tumor  in  the  absence  of  clinical  information. 


235 


ROUND-CELL  SARCOMA. 

Sarcoma  globo-cellulare. 

The  tumor  is  formed  almost  entirely  of  cells  of  variable  size 
and  shape,  whose  general  contour  is  polygonal  or  circular, 
whose  protoplasm  is  abundant  and  without  prolongations, 
whose  nuclei  are  rich  in  chromatin,  and  which  contain  large 
nucleoli.  Sometimes  the  nuclei  are  small,  sometimes  very 
large,  actively  multiplying  and  showing  atypical  mitotic  figures 
or  they  may  even  be  multiple — giant  cells.  The  stroma  consists 
of  occasional  fibrillae  and  abundant  vessels,  with  thin  walls 
composed  only  of  endothelium,  and  often  formed  by  the  cells 
of  the  neoplasm  itself.  Such  a  histological  picture  does  not 
correspond  to  that  of  any  known  organ  and  one  is  brought  to 
the  diagnosis  of  tumor,  which  it  is  always  well  to  confirm  by 
information  from  the  clinic  or  autopsy.  It  is  a  tumor  of  the 
connective-tissue  type  in  which  the  occurrence  of  cell  monstros- 
ities betrays  the  malignant  character. 

It  is  then  a  malignant  tumor  of  the  connective  tissue,  that  is, 
a  sarcoma.  Inasmuch  as  the  cells  are  round,  a  round-cell 
sarcoma,  or  sarcoma  globo-cellulare,  or,  if  the  form  of  the  cells 
is  very  variable,  a  polymorphous  sarcoma. 

Differential  Diagnosis. — Round-cell  sarcoma  must  be  dis- 
tinguished from: 

(a)  Lymphadenoma,  or  lymphocytoma,  which  is  recognized 
by  the  presence  of  a  fine  reticulum  in  the  meshes  of  which 
atypical  lymphocytes  are  contained. 

(b)  Atypical  epithelioma,  which  can  frequently  impose  itself 
upon  us  as  a  sarcoma.     The  differential  diagnosis  is  based  upon 
the  fact  that  the  connective  tissue  and  the  neoplasmic  cells 
are  quite  independent  of  one  another  in  the  epithelial  tumors, 
and  vessels  present  a  normal  wall  quite  independent  of  the 
tissue  of  the  tumor. 

(c)  Inflammatory   pseudo-tumors,    "proud   flesh,"    "granula- 
tion tissue,"  which  present  cells  of  very  polymorphous  char- 
acter, and  in  which  it  is  usually  possible  to  find  the  specific 
lesion — miliary  tubercle,  syphilitic  plasmoma,  etc. 

Resume. — It  is  a  malignant  tumor,  round  or  polymorphous- 
cell  sarcoma,  developed  in  the  subcutaneous  tissue. 


236 


Capillary 

bounded 

by  tumor 

cells. 


Nuclei  in 
strands. 


Frag- 
mented 
nuclei. 


Fig.  108.— Round-cell  sarcoma. 

Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

A  sarcoma  with  extremely  polymorphous  cells  developed  in 
the  cellular  tissue  of  the  thigh,  and  removed  by  surgical  operation. 
It  is  a  tumor  in  which  the  atypical  nature  of  the  cells  and  numerous 
nuclei  showing  mitotic  change  testify  to  extreme  malignancy. 


237 


LYMPHADENOMA. 
Lymphocytoma. 

At  the  center  of  the  drawing,  Fig.  109,  there  is  a  triangular 
section  of  a  capillary  vessel.  From  each  of  its  angles,  con- 
nective-tissue prolongations  extend  and  circumscribe  areas 
in  which  are  cells  and  a  reticulum. 

1.  The  cells,  -pressed  one  against  the  other,  are  lymphocytes, 
the  greater  number  of  which  are  about  the  normal  size,  though 
some  are  large,   with  a.,  greater  amount  of  protoplasm,   and 
nuclei    sometimes   of    monstrous    size,    bilobed   and    showing 
abnormal  karyokinetic  figures. 

2.  The  reticulum  is  often  difficult  to  see,  and  is  formed  of 
connective-tissue  fibrillae,  that  stain  a  rose  color  and  form  an 
immense  network  that  seems  to  be  in  contact  with  the  cells 
either  by  continuity  or  contiguity. 

Such  a  histological  picture — and,  of  course,  it  is  understood 
that  the  rest  of  the  section  has  the  same  general  appearance — 
enables  one  to  recognize  the  lymphoid  tissue,  and  after  eliminat- 
ing the  normal  lymphoid  organs,  to  arrive  at  the  diagnosis  of 
a  lymphoid  tumor. 

Differential  Diagnosis. — The  following  are  to  be  excluded: 

(a)  The  Spleen. — This  organ  is  easily  recognized  by  the  presence 
of   the   Malpighian   corpuscles,   little   collections   of   lymphoid 
tissue  in  the  center  of  which  there  is  usually  a  vessel,  and  by 
its  fibromuscular  trabeculae. 

(b)  The  Lymph  Node. — These  are  composed,  especially  at  the 
periphery,   of  a  pale  tissue   (sinus  lymphaticus)   and  a  dark 
central    or   medullary   substance    with   lymph  follicles   having 
germinati-ve  centers.     Lymph  nodes  subject  to  chronic  inflam- 
mation are  often  difficult  to  differentiate  because  of  the  dis- 
turbance of  the  normal  architecture.     One  then  has  to  look 
with  care  for  such  signs  of  inflammation  as  sclerosis,  poly- 
morphonuclear  leukocytes,  or  for  caseous  centers  with  giant 
cells. 

(c)  The  Thymus,  which  is  easily  recognized  through  the  presence 
of  the  corpuscles  of  Hassal,  formations  roughly  looking  like  the 
bulb  of  an  onion. 

Resume. — It  is  a  tumor  of  a  lymphoid  structure — lymphocy- 
toma, or  lymphadenoma — a  tissue  not  occurring  in  the  normal 
organism. 

It  is  further  an  atypical  tumor,  in  which  nuclear  monstrosities 
betray  malignant  character — malignant  lymphocytoma. 

238 


Normal 
lympho- 
cyte 


Capillary. 


Reticulum 


Fig.  109.— Lymphocytoma. 

Stained  with  hematoxylon  and  eosin.     Magnified  225  diameters. 

This  tumor  was  about  the  size  of  an  egg,  and  grew  in  the  subcu- 
taneous cellular  tissue  of  the  scapular  region.  It  was  surgically 
removed.  The  reticulum  containing  lymphocytes  in  its  meshes  is 
to  be  carefully  noted.  This  network  is  of  extreme  importance  in 
the  differential  diagnosis  of  the  tumor.  The  presence  of  cell 
monstrosities,  though  not  numerous,  betrays  malignant  tendency  of 
the  tumor. 


239 


OSTEOSARCOMA. 
Osteogenetic  Sarcoma. 

The  section,  examined  under  a  low-power  lens,  shows  a 
number  of  long  columns  stained  a  rose-red  color  with  the 
eosin  (osseous  trabeculae),  between  which  are  pale  blue  carti- 
laginous masses  and  connective  tissue  composed  of  elongated 
cells. 

1.  The  Osseous  Trabeculce. — These  are  recognized  by  their 
undifferentiated  and  structureless  substance  (ossein),  in  which 
the  cells  or  osteoplasts ,  of  which  no  more  than  the  nuclei  can  be 
distinguished,  lie  in  spaces. 

Most  of  the  trabeculae  are  surrounded  by  a  border  of  large 
cells — osteoblasts.  These  osseous  formations  do  not  have  a 
medullary  cavity  containing  red  blood  corpuscles  and  hemopoietic 
cells,  or  concentric  arrangements  forming  lamellae  about  a  Haver- 
sian  canal  like  the  normal  bone.  They  consist  rather  of  tissue 
in  process  of  ossification  than  of  fully  formed  bony  tissue. 

2.  The  Cartilaginous  Masses. — These  are  composed  of  homo- 
geneous structureless  pale  masses  of  chondrin,  in  which  are 
cartilage  cells  with  pale  nuclei,  two  or  three  in  a  space. 

3.  The  Fibroblastic  Tissue. — This  is  seen  in  the  left-hand 
upper  part  of  the  drawing  and  consists  of  fusiform  cells  resem- 
bling those  of  the  fibrosarcoma.     Examination  under  the  higher 
power  will  show  cellular  monstrosities. 

Study  of  the  remainder  of  the  section  which  is  found  to 
show  the  same  structure  everywhere  supplemented  by  informa- 
tion from  the  clinic  or  autopsy  brings  us  to  the  conclusion  that 
we  have  to  do  with  a  tumor  of  the  connective  tissues  or  fibro- 
sarcoma. 

But  it  is  a  fibrosarcoma  of  a  special  structure,  inasmuch  as 
it  contains  bone  and  cartilage.  The  young  connective  tissue 
has  manifested  a  peculiar  property  called  metaplasia,  by  which, 
in  the  embryonal  state,  it  transforms  itself  into  other  tissues — 
bone  and  cartilage. 

Resume. — It  is  a  fibrosarcoma  giving  origin  to  bone  and 
cartilage:  ossifying  or  osteogene tic  sarcoma,  observed  exclusively 
in  connection  with  bones. 


240 


Fibro- 

sarcoma- 

tous 

tissue. 


Osseous 
trabecula. 


Cartilage. 


Bundle  of 

fibro- 

blasts. 


Fig.  110. — Osteosarcoma. 
Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

Osteosarcoma  of  the  extremity  of  the  femur  of  a  young  girl  aged 
fourteen  years.  Amputation  at  the  hip-joint;  no  return.  It 
is  an  osteo genetic  sarcoma  showing  in  the  middle  of  sarcomatous 
tissue  fine  osseous  trabecula  and  numerous  masses  of  cartilage  which 
indicate  the  osteogenic  property. 


16 


241 


EPULIS. 
Giant-cell  Sarcoma. 

Examining  under  a  low-power  lens  from  above  downward, 
one  sees  the  following:  A  dark  line  of  stratified  epithelium 
which  corresponds  to  the  external  surface  of  the  structure:  a 
dense  mass  in  which  are  a  large  number  of  large  cells,  multi- 
nucleated  cells,  the  myeloplaxes  a  deep  part  containing  long, 
rose-red  homogeneous  osseous  trabeculae. 

1.  The  Superficial  Epithelium. — This  is  of  the  squamous  type: 
a  deep  basal  germinal  layer  formed  of  parallel  cells,  arranged 
upon  a  basement  membrane,  and  supporting  polyhedral  cells 
with  the  intercellular  filaments  of  Ranvier,  and  surface  cells 
filled  with  granules  of  eleidin,  but  nowhere  showing  a  horny 
formation.     This  type  of  epithelium  is  found  in  the  mouth, 
esophagus,  vulva,  glans  penis,  anus,  etc.    Beneath  the  epithelium 
there  is  a  loose  layer  of  connective  tissue,  the  corium,  which 
contains  the  vessels. 

2.  The   Dense  Tissue  Below  the  Corium. — This  is  formed  of 
fusiform  cells  compactly  placed  one  upon  another,  fibroblasts, 
analogous  to  those  of  fibrosarcoma,  but  without  monstrosities, 
and  without  abnormal  mitotic  figures.     Here  and  there  are 
large  giant  cells,  or  myeloplaxes — large  cells  with  somewhat  baso- 
philic  protoplasm,  and  nuclei  in  varying  numbers,  grouped  in 
masses  in  the  center  or  at  the  periphery.     The  myeloplaxes  must 
not  be  confused  with  the  giant  cells  of  tuberculosis,   whose 
protoplasm  is  distinctly  acidophilic,  and  whose  nuclei  form  a 
peripheral  coronet  like  a  horseshoe. 

3.  The  Osseous  Trabeculce. — These  are  formed  of  lamellae  of 
rose-red  structureless  material:     ossein  containing  osteoplasts. 
Bordering  these  trabeculae  are  the  osteoblasts  which  form  the 
bone.     The  absence  of  organization  in  the  osseous  trabeculae 
(concentric  arrangement  about  Haversian  canals)  suggests  that 
the  structure  is  a  neoplasm. 

Resume. — The  superficial  part  of  the  section  is  composed  of 
a  squamous  mucous  membrane.  The  tumor  is  a  fibroblastic 
tissue  like  that  of  fibrosarcoma,  but  with  the  addition  of  the 
myeloplaxes  and  the  osseous  elements.  It  is  osteosarcoma  of  the 
gum,  a  tumor  described  under  the  name  of  epulis. 


242 


Squamous 
epithe- 
lium. 


Corium. 


Tissue 

with 

myelo- 

plaxes. 


Cells  con- 
taining 
eleidin. 
Cells  of 
the  rete 
mucosum. 


Basal 
cells. 


Corium. 


3  giant 
cells  or 
myelo- 
plaxes. 


Fibro- 
blastic 
tissue. 


Osteo- 

*r      i  &^^*-?rz^j^^^£^-.^-±-^:^^  blasts. 

formed 
bone. 


Osteo- 
plasts. 


Fig.  111. — Epulis.     (Giant-cell  tumor  of  the  gum.) 
Stained  with  hematoxylon  and  eosin.     Magnified  80  diameters. 

Epithelium  and  corium  covering  a  fibroblastic  tissue  with  giant 
cells  and  containing  in  the  center  some  osseous  lamellae.  It  was 
a  tumor  arising  from  the  gum  of  the  mandible  in  a  child  of  eight 
years  that  caused  the  loss  of  two  teeth.  It  was  surgically  removed. 
No  return. 

243 


SQUAMOUS  CELL  CARCINOMA  WITH  EPITHELIAL 

PEARLS. 
Lobulated  Squamous  Epithelioma. 

Diagnosis  of  the  Organ. — Let  the  section  be  examined  with 
a  low-power  lens,  beginning  at  the  left.  The  dark  upper 
border  consists  of  a  squamous  epithelium  with  a  horny  layer 
in  which  can  be  distinguished: 

(a)  The  germinative  layer. 

(b)  The  Malpighian  layers  (rete  mucosum),  composed  of  large 
cells  of  polyhedral  shape,  arranged  in  several  layers  upon  the 
basal  layer. 

(c)  The  granular  layer,  composed  of  cells  filled  with  granules 
of  eleidin. 

(d)  The  horny  layer,  composed  of  cornified  cells — fine  des- 
quamating lamellae  of  keratin. 

Keratinization  of  the  superficial  layers  of  a  squamous  epi- 
thelium can  occur  in  leukoplakia  of  the  buccal  or  vaginal  mucosa; 
but  at  one  extremity  of  the  section  (not  shown  on  the  drawing) 
the  connective  tissue  subjacent  to  this  epithelium  is  found  to 
contain  fat  cells,  which  enable  the  tissue  to  be  recognized  as  the 
skin. 

Diagnosis  of  the  Lesion. — At  the  other  extremity  of  the  draw- 
ing, as  the  cutaneous  epithelium  is  followed  from  left  to  right, 
there  appear  in  the  derm,  enormous  dark-colored  masses  that 
descend  deeply  and  are  separated  more  or  less  completely  by 
islets  and  bands  of  connective  tissue.  They  are  not  in  con- 
tinuity with  the  suprajacent  epithelium,  though  of  a  very 
analogous  structure.  They  are  formed,  at  the  periphery,  of 
cells  whose  appearance  recalls  the  basal  epithelium,  and  at  the 
center,  of  polyhedral  cells  with  intercellular  spines,  of  the 
type  of  the  cells  of  the  Malpighian  layer.  But  that  which 
gives  the  tissue  a  pathognomonic  appearance  is  the  presence, 
in  the  centers  of  the  large  cell  nests,  of  enormous  spherical 
masses,  frequently  malformed,  of  an  ovoid  shape,  the  epithelial 
pearls.  They  are  like  onions  and  are  formed  of  concentric 
laminae  of  cornified  epithelium. 

Between  the  epithelial  masses  is  a  loose  connective  tissue 
which  disappears  little  by  little  as  they  grow,  until  only  narrow 
bands  remain.  This  relation  between  the  stroma  and  the 
cells  is  peculiar  to  malignant  tumors  developed  from  squamous 
epithelium.  The  section  is  one  of  squamous  epithelioma,  lobu- 
lated,  and  containing  epithelial  pearls.  The  epithelium  which 

244 


Derm. 


Epithe- 
lium. 


Infiltra- 
tion of 
neoplas- 
mic  cells. 


Vessels. 


Horny 
layer. 
Rete  mu- 
cosum. 


Epithelial 
pearls. 


Stroma. 


Fig.  112. — Epitheliomaspinocellulare.      (Squamous-cell  carcinoma  with 
epithelial  pearls.) 

Stained  with  hematoxylon  and  eosin.     Magnified  40  diameters. 

A  cutaneous  epithdioma  of  which  a  fragment  was  obtained  at 
autopsy.  Beneath  the  cutaneous  epithelium  with  its  horny  layer 
there  are  numerous  cancer-cell  nests,  some  of  which  contain  epithelial 
pearls. 


245 


covers  the  tumor  is  not  ulcerated:  it  is  the  infiltrating,  not  the 
ulcero-vegetating  variety,  in  which  the  cancer  masses  form 
enormous  buds  that  ulcerate  at  the  surface  and  bleed  upon  the 
slightest  touch. 

A  moderate  magnification  permits  both  the  diagnosis  of  the 
tissue  and  the  lesion  to  be  made :  a  higher  magnification  enables 
the  cytological  details  to  be  studied. 

The  epithelial  cells  contain  numerous  mitotic  figures. 

In  the  neighborhood  of  the  epithelial  pearls  important  trans- 
formations of  the  cells  can  be  seen  and  serve  to  explain  their 
formation.  The  rose-red  center  of  a  young  pearl  (Fig.  113)  is 
composed  of  polyhedral  epithelial  cells  connected  together  by 
protoplasmic  filaments,  the  intercellular  bridges  of  Ranvier, 
which  give  a  stippled  appearance  to  the  interspaces. 

The  nuclei  stain  well  and  are  provided  with  distinct  nucleoli. 
But  in  proportion  as  one  passes  toward  the  center  of  the  pearl, 
the  cells  become  flattened,  attenuated  and  frayed  out  from 
one  another;  their  protoplasm  becomes  paler  and  here  and 
there  small  cavities  with  small  masses  of  chromatin  in  the 
center  are  seen.  This  appearance  is  known  as  dyskeratosis, 
and  has  often  been  mistaken  for  parasitic  inclusions  in  the 
cells.  It  is,  however,  due  to  nuclear  malformation  through 
fragmentation.  Occasional  cells  show  small  dark  blue  dots 
which  take  the  hematoxylon  stain  intensely;  they  are  granules 
of  eleidin  and  precede  the  keratinic  transformation  of  the 
epithelial  cells.  The  cells  flatten  more  and  more,  become 
pale,  almost  acidophilic,  the  nucleus  disappears,  and  nothing 
remains  but  a  mass  of  hyaline  keratinized  substance  surrounded 
by  flattened  cells  arranged  one  upon  another  like  the  skins  of  an 
onion. 

Between  the  cells  and  grouped  around  the  epithelial  pearls, 
occasional  polymorphonuclear  cells,  plasma  cells  and  lympho- 
cytes indicate  secondary  infection,  suggesting  that  there  is  an 
ulceration  of  the  tumor  at  some  point  not  shown  in  the  drawing, 
or  to  be  found  in  the  section. 

Resume. — A  tumor  developed  from  the  squamous  epithelium 
and  recalling  the  structure  and  transformations  of  the  epiderm: 
squamous-cell  epithelioma  with  epithelial  pearls.  A  malignant 
tumor,  because  of  its  destructive  invasion,  the  presence  of  the 
atypical  cells  and  the  frequent  occurrence  of  metastasis  to  the 
regional  lymph  nodes. 


246 


Cells  con- 
taining Nuclear 
Lympho-           eleidin    Cornified      frag- 
cytes.           granules,   center.  ments. 


Spinous 
cells. 


Plasma-     Squamous  Pseudo- 

cytes.  cells.  parasites. 

Fig.  113.— Epithelial  pearl  in  an  epithelioma  of  the  tongue. 


Stained  with  hematoxylon  and  eosin.     Magnified  425  diameters. 

It  is  one  of  the  epithelial  pearls  found  in  the  preceding  section. 
In  this  pearl  the  keratinic  change  is  only  beginning  and  is  far  from 
the  large  formations  that  can  almost  be  seen  with  the  naked  eye. 


247 


CARCINOMA  BASOCELLULARE. 
Tubular  Squamous-cell  Carcinoma — Rodent  ulcer. 

Diagnosis  of  the  Organ. — The  preparation  can  be  divided 
into  two  parts;  that  on  the  left,  in  which  the  organ  can  be 
recognized,  and  that  on  the  right,  which  shows  the  lesion. 

In  the  left-hand  portion  are  found  elements  characteristic 
of  the  skin:  squamous  epithelium  with  a  uniform  horny  layer, 
supported  upon  a  dense  connective  tissue  in  the  thickness  of 
which  are  numerous  fat  cells;  sebaceous  glands,  with  their 
large  pale  cells  grouped  in  masses  and  filled  with  fine  granules 
of  fat;  sudoriparous  glands  with  a  double  row  of  nuclei  in 
the  lining,  myoepithelium;  hairs  cut  obliquely  and  provided 
with  an  epithelial  sheath. 

Diagnosis  of  the  Lesion. — At  the  right-hand  extremity  of  the 
drawing,  beneath  the  epithelium,  there  appear  in  the  connec- 
tive-tissue stroma  below  and  without  the  least  ulceration,  large 
masses  of  dark  blue  which  the  connective  tissue  divides  into 
more  or  less  distinct  tubular  formations.  This  infiltration  of 
the  corium  by  the  epithelium,  without  distinct  limits,  indicates 
a  malignant  tumor,  epithelioma. 

But  the  uniformity  of  the  cells  which  compose  its  prolonga- 
tions and  the  complete  absence  of  epithelial  pearls  cause  this 
tumor  to  appear  quite  different  from  the  epithelioma  shown 
in  Fig.  112. 

Under  a  higher  power  magnification,  the  tumor  is  found  to 
be  composed  chiefly  of  cells  recalling  those  of  the  basal  layers 
of  the  epiderm;  cells  uniform  in  their  structure  and  not  subject 
to  keratinic  change.  Everywhere  the  protoplasm  has  the 
same  staining  quality,  and  nowhere  do  granules  of  eleidin 
occur  in  the  cells.  Occasional  monstrous  cells  may  be  found. 

The  absence  of  all  keratinic  transformation  and  the  close 
resemblance  of  the  cells  of  the  neoplasm  to  those  of  the  basal 
layer  of  the  epiderm  lead  one  to  designate  the  tumor  an  epithe- 
lioma basocellulare.  It  is  sometimes  called  tubular  epithelioma 
because  of  the  tube-like  arrangement  of  its  cell  processes. 

The  connective-tissue  stroma  shows  an  enormous  infiltra- 
tion of  leukocytes  in  consequence  of  suprajacent  infection. 

Resume. — An  epithelial  tumor  derived  from  the  basal  or 
germinal  layers  of  the  epithelium — an  epithelioma  basocellulare. 


248 


Trans- 
verse 
section  of 

Interpapil-  an  elon- 
lary  pro-      gated 


Rete 


longation.  papilla,     mucosum. 


Horny        Cancer 
layer.        masses. 


Sebaceous 
gland. 


Sweat 
gland. 


Smooth 
muscle 
fibers. 


Stroma. 


Fig.  114. — Epithelioma  basocellulare  of  the  skin. 
Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

//  is  a  section  of  a  cancroid  or  rodent  ulcer  of  the  cheek,  removed 
at  operation.  This  form  of  epithelioma  differs  from  the  preceding 
in  the  absence  of  the  epithelial  pearls  and  the  nature  of  the  cells 
from  which  the  tumor  arises.  In  the  middle  and  to  the  left  of 
the  drawing  there  is  a  little  fasciculus  of  smooth  muscle  fibers— one 
of  the  arr actor es  pilaris  connected  with  the  hairs. 


249 


NEVUS  OF  THE  SKIN. 

Melanotic  Tumor.    Nevo-carcinoma. 

Diagnosis  of  the  Organ. — When  the  section  is  examined 
under  a  low-power  lens,  it  is  found  to  be  composed  of  two 
distinct  parts;  one  superficial,  consisting  of  a  narrow  dark 
bluish  band;  the  other,  deeper  and  more  extended,  of  an 
extremely  dense  tissue.  The  dark  band  that  borders  the  upper 
part  of  the  drawing  is  a  squamous  epithelium  in  which  can  be 
found  a  basal  germinative  layer,  successive  strata  of  polygonal 
cells,  a  granular  layer  and  a  covering  of  horny  cells.  This 
type  of  structure  together  with  the  presence  of  fat  cells  in  the 
subjacent  connective  tissue  characterize  the  skin. 

Diagnosis  of  the  Lesion. — The  enormous  dark  mass  that  make 
up  the  greater  part  of  the  section  is  part  of  a  tumor  whose 
structure  is  almost  unique. 

It  is  composed  of  elongated  cells  arranged  in  whorls  and  is 
provided  with  a  large  number  of  newly  formed  bloodvessels. 
The  appearance  recalls  that  of  the  fibrosarcoma,  and  easily 
leads  to  an  erroneous  diagnosis. 

These  cells  are  intermediate  between  the  epithelial  and  the 
connective  tissue  types,  and  are  called  nevus  cells,  because 
they  are  found  only  in  congenital  tumors  or  malformations  of 
the  skin — the  new. 

But  that  which  gives  the  section  its  most  unusual  appear- 
ance is  the  presence  of  pigment  in  granular  masses  of  brown 
color  and  irregular  form.  Nearly  all  of  the  cells  also  contain 
a  large  number  of  minute  black  granules. 

This  is  a  peculiar  pigment,  melanin,  which  is  not  derived 
from  the  blood  pigment  (hematoidin) . 

The  presence  of  the  elongated  cells,  young  and  of  an  embry- 
onal appearance,  and  the  great  abundance  of  the  pigment 
masses  in  the  neighborhood  of  the  skin,  indicate  a  tumor  devel- 
oped from  the  nevus  and  pigment  cells,  the  chromatophores , 
which  are  also  found  in  the  normal  skin — the  pigmented  nevus. 

Such  melanotic  tumors  can  be  either  benign — nevus  pig- 
mentosus  (birthmarks,  beauty  spots,  etc),  or  malignant.  In  the 
latter  case  they  develop  rapidly  and  cause  numerous  metastases : 
new-carcinoma. 


250 


Skin. 


Tumor. 


Epithe- 
lium. 

Connec- 
tive tissue 
of  derm. 

Vessel. 


Hair. 

Inflam- 
matory 
cellular 
infiltra- 
tion. 


Nevus  cells. 


Cells  pigmented 
with  melanin. 


Melanin  masses. 


Fig.  115. — Nevus  of  the  skin 

A. — Shows  the  skin  and  the  suprajacent  tumor,  magnified  60 
diameters. 

B.— Shows  the  cells  and  the  crowded  masses  of  melanotic  pig- 
ment, magnified  200  diameters. 

251 


CHORION-EPITHELIOMA. 

Syncytioma  Malignum. 

Diagnosis  of  the  Organ. — From  the  portion  of  the  tumor 
shown  in  the  drawing  it  is  impossible  to  discover  from  what 
organ  the  section  comes,  because,  as  so  commonly  happens  in 
practice,  the  section  is  of  a  fragment  removed  from  the  uterus 
with  a  curette  and  contains  none  of  the  tissue  of  the  organ 
from  which  it  came. 

Diagnosis  of  the  Lesion.  — Examination  shows  that  the  histo- 
logical  structure  of  the  tissue  does  not  correspond  with  any 
organ  of  the  body.  Under  these  circumstances  the  possibility 
of  tumor  should  be  kept  in  mind. 

If  we  are  informed  that  the  tissue  under  examination  is  part 
of  the  proceeds  of  a  uterine  curettement,  the  possibility  of  its 
being  embryonal  should  be  considered. 

A  medium-power  lens  shows  the  section  to  consist  mainly  of 
nondescript  cells  unlike  in  size  and  appearance,  and  lacking 
definite  arrangement.  They  are,  however,  resolvable  into  two 
principal  varieties: 

1.  Pale  Cells.—  When  these  are  most  distinct  they  appear  of 
cuboidal  shape,   the  surfaces  of  contact  clearly  marked,  the 
nuclei  vesicular  and  palely  staining,  the  cytoplasm  pale,  some- 
times slightly  granular  or  vacuolated.     But  these  cells  are  not 
always  clearly  outlined  and  separated  from  one  another;  instead 
many  of  them  are  indistinctly  outlined,  and  not  infrequently 
great  numbers  of  them  are  fused  together  into  an  indefinite 
plasmodium  which  may  fade  away  into  necrotic  areas  in  which 
deformed  and  gigantic  nuclei  are  common. 

2.  Dark  Cells.—  These  are  rarely  distinct  cells,  but  rather 
giant  cells  and  masses  of  nucleated  protoplasm.     Their  outlines 
are  sometimes  distinct,  but  sometimes  fade  away  into  neighbor- 
ing protoplasmic  masses  either  of  the  same  kind  or  of  the  pale 
kind.     The  cytoplasm  of  these  cells  and  masses  is  distinctly 
basophilic  and  the  nuclei,  which  vary  in  size  and  shape,  are 
usually  deep  staining. 

In  addition  to  the  cells  and  cell  masses  described,  sections 
of  this  tumor  usually  show  extensive  necrosis  and  hemorrhagic 
infiltration. 

The  structure  shown  and  described,  even  in  the  absence  of 
chorionic  villi,  which,  of  course,  would  be  pathognomonic  of 
retained  secundines,  is  sufficient  to  enable  a  diagnosis  of  embry- 
onal tissue  to  be  made. 

252 


The  pale  cells  may  be  decidual,  when  they  descend  from  the 
maternal  tissue,  or  chorionic  (cells  of  Langhans),  when  they  are 
embryonal. 

The  dark  cells  are  syncytial  and  embryonal  and  descend 
from  the  trophoblast. 

In  cases  of  retained  secundines,  the  cells  mentioned  not  infre- 
quently proliferate,  and  the  syncytium,  whose  primary  function 
seems  to  be  to  erode  the  decidua  and  open  the  uterine  blood 
sinuses  to  the  chorionic  villi,  may  descend  deeply  into  the 
uterine  wall.  Such  abnormality  results  in  a  highly  necrotic 
and  hemorrhagic  tissue  mass  classified  as  a  tumor.  If  it  remains 
local,  and  eventually  disappears  by  necrosis  or  fails  to  reappear 
after  removal  by  the  curette,  it  is  benign  chorion-epithelioma  or 
syncytioma  benignum.  If,  on  the  other  hand  it  continues  to 
invade  the  uterine  wall  through  the  erosive  action  of  the  growing 
syncytium,  and  entering  into  the  bloodvessels  becomes  dissemi- 
nated to  other  organs,  a  highly  destructive  and  fatal  tumor, 
malignant  chorion-epithelioma  or  syncytioma  malignum  results. 
The  microscopic  examination  of  a  fragment  may  not  be  sufficient 
to  enable  the  malignant  nature  of  the  growth  to  be  determined. 

Resume.  —A  morbid  growth  of  embryonal  tissue  derived  from 
the  foetal  membranes,  composed  chiefly  of  chorionic  and  syn- 
cytial cells — syncytioma  malignum. 


Syn- 
cytium. 


.* 


:i>*  "•'»V'^    * 


Chorionic 
cells  or 
cells  of 
Langhans. 


Syn- 
cytium. 


Fig.  116. — Chorionic  epithelioma  or  syncytioma  malignum. 
253 


SACRO-COCCYGEAL  TUMOR. 

Mixed  Tumor  of  the  Sacro-coccygeal  Region. 

The  section  when  examined  under  a  low  power  presents  an 
extraordinary  polymorphous  appearance  whose  structure  does 
not  suggest  any  known  organ.  It  is  in  reality  an  extremely 
complex  tumor,  produced,  so  to  speak,  through  the  juxtaposi- 
tion of  several  different  elementary  tissues.  Examined  under 
a  medium  power,  the  different  tissues  of  which  it  is  composed 
can  be  studied: 

(a)  Dark-colored    formations    suggesting    glandular    acini. 
These  are  lined  with  an  epithelium,  not  unlike  that  of  the 
mammary  gland,  the  thyroid  body  or  the  tubules  of  the  kidney. 

(b)  Certain  of  them  are  cystically  dilated,  and  all  intermediate 
stages  between  acini  and  cysts  can  be  found.     The  cysts  are 
lined  by  a  more  or  less  flattened  epithelium  that  is   rarely 
stratified,  and  contain  a  fluid  in  which  occasional  cells  with 
pycnotic  nuclei  (not  shown  in  the  drawing)  are  suspended. 

(c)  The   stroma   surrounding   these   formations   is   a   loose, 
more  or  less  nucleated  connective  tissue,  some  areas  in  which 
are  infiltrated  with  fat.     As  the  glandular  formations  at  such 
points   have   very   indistinct   limitations,    and    the   basement 
membrane  is  frequently  absent,  the  histological  appearance  is 
suggestive  of  sarcoma  so  far  as  the  interstitial  tissue  is  con- 
cerned, and  of  carcinoma  so  far  as  the  glandular  elements  are 
concerned.     The  absence  of  the  basement  membrane  and  the 
dispersion   of   the   epithelial   cells   in    the    cellular   connective 
tissue  may  suggest  the  diagnosis  of  adenosarcoma. 

(d)  In   the  stroma,   and  adding  to   the  complexity  of  the 
tumor,  may  be  found: 

1.  Striated  muscular  fibers  cut  transversely  or  longitudinally, 
and  easily  recognized  by  their  peripheral  nuclei. 

2.  Cartilaginous  masses,  forming  homogeneous  blue-staining 
areas  with  numerous  retracted  cells  enclosed  in  spaces  in  the 
chondrous  substance  (chondrin). 

Resume.— The  number  and  variety  of  formations  and  tissues 
lead  to  the  conclusion  that  it  is  a  mixed  tumor— SL  tumor  of 
multiple  tissues  of  congenital  origin— an  embryoma. 


254 


Cartilage. 


Striated 
muscle. 


Cyst. 


Acinus. 


Fig.  117. — Mixed  tumor  of  the  sacro-cocygea!  region.     Embryoma. 

Stained  with  hematoxylon  and  eosin.     Magnified  50  diameters. 

A  sacro-coccygeal  tumor  about  the  size  of  an  orange  taken  from 
an  infant,  aged  one  year,  by  resection  of  a  part  of  the  sacrum. 
Multiple  sections  made  from  different  parts  all  showed  structure 
identical  with  that  represented  in  the  drawing. 


255 


INTRADERMIC  ABSCESS. 
Streptococcic  Abscess. 

The  section  passes  through  an  entire  small  abscess  situated 
beneath  the  skin.  When  it  is  examined  under  a  low  power 
(Fig.  118,  A),  it  is  found  to  be  bordered  on  one  side  by  a  narrow 
blue  band  (stained  with  hematoxylon)  covering  a  loose  con- 
nective tissue.  Below  this  is  a  large  rounded  mass,  stained 
red-violet,  in  the  center  of  which  is  an  excavation. 

Diagnosis  of  the  Organ. — Under  a  medium  magnification 
(Fig.  118,  A),  the  dark  blue  line  can  be  recognized  as  a  squa- 
mous  epithelium  with  a  basal  germinative  layer,  a  mucous 
body  of  Malpighi,  elongated  cells  containing  eleidin,  and  a 
cornified  layer  formed  of  thin  desquamating  plates. 

This  epithelium  rests  upon  a  dense  connective  tissue,  the  derm, 
in  which  hairs,  sebaceous  glands  and  sweat  glands  (not  shown 
in  the  drawing)  can  be  found.  The  cornified  epithelium  and 
the  presence  of  fat  cells  below,  enable  the  skin  to  be  recognized. 

Diagnosis  of  the  Lesion  (Fig.  118,  A). — The  epithelium  is 
normal.  The  derm  alone  contains  the  lesion  in  the  form  of 
a  rounded  mass.  The  periphery  of  this  nodule  is  formed  by  a 
thick  sheath  of  inflammatory  cells  with  several  patches  of  red 
stained  substance — small  hemorrhages.  About  the  nodule  there 
is  a  loose  connective  tissue,  rich  in  fatty  vacuoles,  with  a  light 
infiltration  of  inflammatory  cells,  giving  the  connective-tissue 
trabeculae  a  darkly  dotted  appearance.  The  center  of  the 
nodule  contains  an  agglomeration  of  cells  to  see  the  structural 
details  of  which  it  is  necessary  to  employ  a  high  power,  even 
an  oil-immersion  lens.  The  zones  marked  by  the  small  rect- 
angles i,  2  and  3,  on  the  drawing  A,  should  be  studied  in  detail. 

Zone  i  (Fig.  118,  B).— The  debris  which  lies  in  the  center 
of  the  cavity,  and  the  thin  layer  lining  it,  are  composed  of  cells 
with  lobulated  nuclei,  relatively  abundant  protoplasm  brightly 
stained  with  eosin,  and  without  easily  recognized  granules. 
These  are  polymorphonuclear  leukocytes.  Their  enormous 
number  is  an  indication  of  acute  inflammation.  The  fragmenta- 
tion of  the  nuclei,  the  loss  of  chromatic  details  (chromatolysis) 
and  the  eosin  affinity  of  the  protoplasm  show  it  to  be  an  abscess. 
In  the  interior  of  some  of  the  cells  it  may  be  possible  to  find 
some  of  the  microorganisms  of  suppuration  (streptococcus, 
staphylococcus,  etc.),  hence,  the  name  phagocytes  and  for  these 
cells  in  particular,  micro phages.  Beyond  the  microphages,  in 
the  inferior  part  of  the  drawing  (B)  and  frequently  mixed  with 

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them,  are  a  number  of  larger  cells  with  finely  granular  proto- 
plasm, containing  besides  the  nucleus,  chromatin  fragments 
and  sometimes  even  a  polymorphonuclear  leukocyte.  This  is 
another  manifestation  of  phagocytosis — pyophagocytosis — these 
cells  being  known  as  pyophages.  The  polynuclears  and  pyo- 
phages may  be  held  by  delicate  threads  of  fibrin  or  simply 
immersed  in  a  fluid  which  constitutes  the  most  internal  part 
of  the  inflammatory  nodule,  the  part  completely  liquefied,  the 
pus  of  the  abscess. 

Zone  2  (Fig.  119,  C). — Outside  of  the  layer  of  the  pyophages 
is  a  zone  of  organized  tissue,  rich  in  newly  formed  vessels,  and 
in  large  mononucleated  cells  of  a  form  intermediate  between 
the  polynuclears  and  the  pyophages.  These  are  the  large 
mononuclear  cells,  macrophages,  some  of  which,  in  a  state  of 
degeneration,  show  protoplasm  that  is  homogeneous  and  acido- 
philic  and  have  pycnotic  nuclei. 

Besides  the  macrophages  there  are  a  large  number  of  cells  of 
oval  form  with  polar  nuclei,  the  plasmacytes.  These  can  multi- 
ply as  is  shown  by  the  presence  of  several  nuclei  in  some  of 
them.  The  much  dilated  bloodvessels  show  a  thickened  endo- 
thelium.  In  a  capillary,  shown  in  the  central  part  of  the 
drawing,  red  blood  corpuscles  and  two  polymorphonuclear 
leukocytes  indicate  coexistent  leukocytosis. 

Zone  3  (Fig.  119,  D).— The  upper  part  of  this  zone  is  a  con- 
tinuation of  the  preceding.  There  are  three  capillaries  and 
numerous  mononuclears  and  plasmacytes.  In  the  lower  part 
the  confines  of  the  pyogenic  membrane  are  reached.  There 
are  a  number  of  fibroblasts  that  have  formed  collagen  fibers. 
In  the  interstices  are  some  large  mononuclears  and  some  plas- 
macytes. 

Resume.— In  this  section  can  be  followed  in  detail  all  of  the 
stages  of  an  acute  inflammation:  cellular  necrosis,  extremely 
active  phagocytosis,  and  finally  the  connective-tissue  reaction. 
The  abscess  is  sharply  circumscribed  by  an  important  con- 
nective tissue  reaction  that  tends  to  limit  the  extension  of  the 
suppuration  and  make  it  different  from  the  diffuse  phlegmon 
and  the  cold  abscesses  of  tuberculosis. 


258 


Macro- 
phage. 


Plasma- 
cyte. 

In- 
flamed 
newly 
formed 
vessel. 
Poly- 
morpho- 
nuclear 
leukocytes. 
Mitosis. 


Capillary. 

Mononu- 
clear 
leuko- 
cytes. 


Capillary. 

Plasma- 
cyte. 


Capillary. 


Fibro- 
blast. 


PI  asm  a- 
cytes. 


Fig.  119. — Intradermic  abscess. 


C.—Zone  2  (Fig.  118)  showing  the  macrophagic  reaction,  the 
plasmacytes  and  the  newly  formed  capillary  vessels  with  swollen 
endothclium. 

D.—Zone  3  (Fig.  118)  showing  the  fibroblastic  reaction  forming 
pyogenic  membrane  at  the  outer  limits  of  the  abscess. 


259 


SUBCUTANEOUS  SPOROTRICHOTIC  NODULE. 

Diagnosis  of  the  Organ.— An  examination  of  the  specimen 
with  the  naked  eye,  and  a  low-power  lens  (Fig.  120,  A),  shows 
that  the  section  passes  through  an  entire  subcutaneous  nodule. 

The  presence  of  squamous  epithelium  with  its  various  layers 
of  hair  follicles  and  sebaceous  glands  are  sufficient  to  make  the 
diagnosis  of  the  skin. 

Diagnosis  of  the  Lesion. — In  the  thickness  of  the  derm  and 
subcutaneous  tissue  there  is  a  dark  blue  colored  nodule,  in  the 
center  of  which  there  is  an  irregular  space.  It  is  a  circum- 
scribed new  formation  concerning  the  exact  nature  of  which  it 
will  require  a  higher  magnification  to  decide. 

The  Central  Zone  (Fig.  120,  B;  No.  i  in  Fig.  120.  A).— This  is  a 
zone  of  suppuration  as  is  shown  by  the  large  number  of  cells  with 
polylobed  nuclei,  relatively  abundant  protoplasm  colored  dis- 
tinctly by  the  eosin,  and  without  appreciable  granules.  They 
are  polymorphonuclear  leukocytes  in  a  more  or  less  marked 
condition  of  necrosis,  and  forming  the  pus  cells  or  pyocytes. 
The  fragmentation  of  the  nuclei,  the  chromatolysis,  the  eosino- 
philia  of  the  protoplasm  are  characteristic  of  pus  cells  and  are 
the  same  as  in  the  more  common  form  of  suppuration  already 
studied. 

At  the  periphery  of  this  central  zone  the  lower  part  of  Fig. 
1 20,  B,  pyophages  are  mixed  with  the  pyocytes.  As  in  the 
abscess,  the  pyophages  and  polymorphonuclears  may  be  held 
by  a  fine  fibrinous  reticulum,  or  be  suspended  in  the  fluid  in  the 
cavity. 

As  the  examination  proceeds  from  the  center  to  the  periphery 
the  pyophages  become  more  and  more  rare  until  they  disappear 
altogether,  and  a  growing  connective  tissue  is  reached.  It  is 
composed  of  fibroblasts  in  process  of  metaplasia.  The  collagen 
fibers  are  nearly  all  absorbed,  and  scarcely  anything  remains 
except  fine  fibrillae  more  or  less  dissociated  by  edematous  fluid. 
Between  fibers  and  fibroblasts  occasional  polymorphonuclear 
cells  with  pycnotic  nuclei  may  be  found. 

The  Intermediate  Zone  (Fig.  121,  C;  No.  2,  Fig.  120,  A).— This 
is  the  zone  of  epithelioid  and  giant  cells.  The  drawing  shows  a 
number  of  cells  with  pale  nuclei  and  scarcely  stained  protoplasm 
with  peripheral  prolongations,  and  two  giant  cells;  one  in  the 
center  of  the  figure,  containing  two  nuclei,  the  other  at  the 
lower  part — left-hand  part — with  a  pale  center  in  the  early 
stage  of  necrosis,  and  a  coronet  of  nuclei  at  the  periphery. 

200 


Fig.  120. — Subcutaneous  sporotrichotic  nodule. 
Stained  with  hematoxylon  and  eosin. 

A.— View  of  the  entire  section,  magnified  3  diameters,  showing 
in  the  little  rectangles  i,  2,  3  the  areas  jrom  which  the  following 
drawings  were  made  under  a  higher  power. 

E.—Zone  i,  magnified  350  diameters,  showing  the  pus  cells 
in  the  center  of  the  abscess,  and  the  zone  of  macrophages  outside. 


261 


Scattered  among  these  are  also  a  number  of  mononuclear 
and  polynuclear  cells  and  occasional  fibroblasts. 

Peripheral  Zone  (Fig.  121,  D;  No.  3,  Fig.  120,  A).— This  cor- 
responds to  the  external  limiting  zone  of  the  sporotrichotic 
nodule.  In  it  appear  plasmacytes  which  have  an  ovoid  shape, 
basophilic  cytoplasm,  especially  dark  at  the  periphery  and  polar 
nuclei  which  are  spherical  and  have  a  reticulated  appearance, 
and  large  granules  of  chromatin  pressed  against  the  nuclear 
membrane  or  about  the  micleolus  which  is  usually  quite  distinct. 
The  nuclei  appear  in  the  center  or  at  the  pole  of  the  cells  accord- 
ingly as  they  are  cut  tangentially  or  perpendicularly. 

Sometimes  a  plasmacyte  may  have  two  or  three  nuclei,  indi- 
cating cellular  division. 

There  are  also  sections  of  capillaries,  indicating  vascularity. 
Their  walls  are  formed  of  several  layers  of  cells,  the  endothelium 
being  tumified  or  swollen,  unlike  the  normal  condition  in  which 
they  simply  show  a  single  layer  of  endothelial  cells. 

In  the  most  external  zone  (lower  part  of  the  Fig.  121,  D), 
the  pyogenic  membrane  is  seen  to  form  the  external  limit  of 
the  nodule.  It  is  composed  of  fibroblasts  and  collagen  fibers 
more  or  less  dense,  in  the  interspaces  of  which  are  a  few  lympho- 
cytes and  polymorphonuclears. 

Resume. — An  intradermic  inflammatory  nodule  composed  of 
three  zones  of  inflammatory  reaction  of  different  character: 

A  central  zone,  composed  of  pus  formed  of  degenerated  poly- 
morphonuclear  cells  and  pyophagous  mononuclears  of  large  size. 

A  median  zone  with  epithelioid  and  giant  cells,  recalling  the 
lesions  of  miliary  tuberculosis. 

A  peripheral  zone,  intensely  vascular,  composed  of  lymphocytes 
and  plasma  cells.  This  histological  structure  is  sufficiently 
characteristic  to  permit  the  diagnosis  of  sporotrichosis  to  be 
made.  But  besides  this  a  bacteriological  examination  by  cul- 
tures from  the  fresh  material  ought  to  be  made,  and  should 
show  the  specific  agent,  the  sporotrichium  of  Beurmann  and 
Gougerot. 


262 


Poly- 

morpho- 

nuclears. 

Epithelial   ^ 
cells. 


Giant 
cells. 


Plasma- 
cytes. 


Mononu- 
clears. 

Giant 
cells. 

Fibro. 
blasts. 


Fig.  121.— Subcutaneous  sporotrichotic  nodule. 


Collagen 
fibers. 


C. — Zone  2  showing  giant  cells  and  epithelioid  cells. 
D. — Zone  3  showing  the  lymphocytic  resection  in  the  connective 
tissue  and  the  vascularity  of  the  pyogenic  membrane. 


263 


BLOOD  CAPILLARIES  IN   INFLAMMATION. 

The  drawing  shows  a  collection  of  blood  capillaries  such  as 
are  frequently  met  with  in  various  normal  and  pathological 
conditions. 

Fig.  122,  A  and  B,  show  two  different  stages  in  the  embryo- 
genesis  of  blood  capillaries. 

A  is  connective  tissue  taken  from  an  embryo.  In  the  middle 
of  an  extremely  loose  tissue  of  a  myxoid  appearance,  and  com- 
posed of  undifferentiated  connective-tissue  cells,  there  is  a 
section  of  a  long  tube,  cut  longitudinally  at  the  left  and  trans- 
versely at  the  right.  Such  cellular  tubes,  from  which  the 
vascular  system  is  developed,  are  the  islands  or  cords  of  Wolf 
of  the  embryologists. 

In  B  is  shown  an  embryonal  capillary  developed  from  a  cord 
of  Wolf,  in  the  center  of  which  is  a  lumen.  Its  walls  consist  of 
endothelial  cells  with  large  nuclei  which  project  into  the  lumen 
in  which  there  is  a  nucleated  red  blood  corpuscle:  normoblast. 
The  connective  tissue  about  the  capillary  has  acquired  a  more 
dense  appearance  than  that  shown  in  Fig.  122,  A. 

Capillaries  with  such  embryonal  appearance  are  frequently 
found  in  the  adult  in  pathological  conditions,  especially  in  the 
course  of  inflammatory  disturbances  such  as  proud  flesh. 

In  Fig.  122,  C,  is  shown  a  section  of  adult  capillary  in  a 
dense  connective  tissue. 

The  wall  is  formed  of  a  single  layer  of  endothelial  cells  very 
flattened,  in  which  two  fusiform  nuclei  can  be  seen.  The  lumen 
contains  six  or  seven  red  blood  corpuscles  of  the  adult  type. 

The  connective  tissue  through  which  the  capillary  passes  is 
sclerotic:  in  it  there  are  very  few  cells  (fibroblasts)  and  very 
many  collagen  fibers. 

In  Fig.  122,  D,  is  shown  a  capillary  in  an  inflamed  tissue. 
Diapedesis  of  leukocytes  is  distinct.  It  consists  in  the  passage 
of  the  polymorphonuclear  and  small  mononuclear  white  blood 
corpuscles  through  the  wall  of  the  capillary  vessel.  In  the 
drawing  is  shown  the  condition  known  as  margination  of  leuko- 
cytes, that  is  to  say,  their  attachment  to  the  inner  wall  of  the 
vessel,  and  their  passage  through  it  into  the  neighboring  stroma. 


264 


Wolffian 
cord. 


Poly- 
morpho- 
nuclears. 
Red  blood 
corpuscles. 
Endo- 
thelium. 
Connec- 
tive tissue 
fibers. 


B 


(  'iilMHV- 

j^_-£«£ — __|_  tivc  1  issue 
.      ,,.11 


D 

Connective 
tissue  fibres. 

Polymorpho- 
nuclears. 


*  Mononuclears. 
Endothelium. 


ljRfl^H3B  '    Mononuclear. 


Fig.  122.— Capillary  bloodvessels. 
Stained  with  hematoxylon  and  eosin.     Magnified  350  diameters. 

A.— Embryonal  capillary  showing  the  cords  of  Wolf. 
B. — Embryonal  capillary  containing  a  normoblast. 
C.— Adult  capillary  in  sclerosed  tissue. 

D. — Capillary  in  inflammed  tissue  showing  the  margination  of 
leukocytes  and  diapedesis  of  white  corpuscles. 


265 


SYPHILITIC  CHANCRE. 

Diagnosis  of  the  Organ.— If  in  this  case  it  is  not  possible  to 
determine  with  what  organ  one  has  to  do,  he  can  say  very 
definitely  that  it  is  a  squamous  epithelium  of  which  a  basal 
germinative  layer,  a  rete  Malpighii  and  horny  scales  in  process 
of  desquamation  can  be  recognized. 

No  fat  cells  are  found  in  the  subjacent  tissue,  nor  are  there 
any  sebaceous  glands,  sweat  glands  or  hair  follicles.  It  is  the 
prepuce. 

Diagnosis  of  the  Lesion.— Below  the  epithelial  covering,  inter- 
rupted over  a  considerable  part  of  its  extent,  by  an  ulceration, 
there  is  a  dark  bluish  mass  which  constitutes  the  principal  lesion. 
It  is  shown  by  a  blue  stippling  that  indicates  numerous  cells 
and  a  large  number  of  capillary  vessels,  all  lost  in  a  pale  rose 
connective  tissue.  The  stippling  and  the  vessels  are  distinctly 
shown  in  Fig.  123,  B.  With  such  a  magnification  it  is  difficult 
to  determine  further  details,  except  a  very  definite  collection 
of  the  cells  about  the  vessels.  A  much  greater  magnification, 
even  an  oil-immersion  lens  may  be  necessary  to  bring  out  the 
nature  of  the  lesion. 

Let  one  of  the  capillaries  with  its  perivascular  infiltration 
(Fig.  124)  be  studied. 

In  the  center  of  the  drawing  is  a  capillary  with  a  distinctly 
thickened  wall  and  swollen  endothelium  projecting  into  the 
lumen,  and  partly  obstructing  it.  The  external  wall  is  also 
proliferated  and  is  composed  of  several  layers  of  young  con- 
nective-tissue cells.  An  intense  vasculitis  is  expressed  by  the 
scantiness  of  the  lumen  in  comparison  with  the  thickness  of  the 
wall. 

About  the  capillary  the  infiltration  consists  of  large  oval  cells 
with  excentric  nuclei— plasmacytes— which  indicate  a  particular 
type  of  inflammatory  reaction  which  is  sometimes  called  "plas- 
moma  perivasculare." 

Though  very  numerous,  the  plasmacytes  do  not  constitute  the 
only  cells  in  the  inflammatory  infiltration.  There  are  also  a 
considerable  number  of  lymphocytes,  and  occasional,  but  rare, 
polymorphonuclears,  and  lastly  forms  intermediate  between  the 
plasmacytes,  the  lymphocytes  and  the  mononuclears. 

The  plasmoma  characterizes  the  primary  and  secondary 
lesions  of  syphilis;  but  it  is  not  specific  as  it  is  quite  possible 
to  find  similar  infiltrations  of  plasmacytes  in  other  types  of 
inflammation,  as  in  sporotrichosis  for  example. 

266 


Ulceration. 


Epithelium 
of  the 
prepuce. 


B 


Ulceration. 


Capillary 
with  peri- 
vascular 
infiltra- 
tion. 


Epithe- 
lium. 


Stroma. 

Lymph- 
angitis. 


Capillaries. 


Fig.  123. — Syphilitic  chancre  of  the  prepuce. 

Stained  with  hematoxylon  and  eosin. 

Operative  removal  of  the  prepuce  in  the  early  days  of  the  develop- 
ment of  the  chancre. 

A.— Showing  the  entire  ulceration,  magnified  20  diameters. 

B.— Showing  the  inflammatory  infiltration  about  the  bloodvessels 
of  the  stroma,  magnified  40  diameters. 

267 


The  stroma  contains  large  fibroblasts  with  normal  appearing 
nuclei,  and  protoplasm  which  has  secreted  an  abundance  of 
collagen  fibrillas,  which  give  the  lesion  (the  chancre)  its  induration. 

Resume.— Because  of  the  nature  of  the  cells  that  go  to  make 
up  the  cellular  infiltration,  and  their  arrangement  about  the 
bloodvessels  as  well  as  the  importance  of  the  vascular  lesions, 
it  is  correct  to  make  a  diagnosis  of  primary  or  secondary  syphilis; 
a  diagnosis  to  be  confirmed  later  by  the  discovery  of  the  trepon- 
ema  through  the  employment  of  one  of  the  special  methods  of 
staining  with  silver  salts. 


Plasma- 
cytes. 


Dividing 

plasma- 

cytes. 


Poly- 
morpho- 
nuclears. 


Mononu- 
clears. 


Fig.  124. — Syphilitic  chancre  of  the  prepuce. 


Stained  with  hematoxylon  and  eosin.     Magnified  425  diameters. 


One  of  the  capillaries  s'hown  in  the  preceding  drawing  is  shown 
under  a  higher  magnification  to  show  the  plasmacytic  perivascular 
infiltration.  Note  the  thickness  of  the  wall  of  the  capillary,  in  which 
the  endothelial  cells  are  swollen  and  surrounded  by  several  layers 
of  fibroblasts.  About  the  capillary  the  tissue  is  infiltrated  with  a 
composition  of  inflammatory  cells  particularly  rich  in  plasmacytes. 

268 


INDEX  TO  THE  ILLUSTRATIONS. 


ABSCESS,  biliary,  of  liver,  Fig.  32, 

P-  85 
embolic,  of  kidney,  Fig.  61,  p. 

143;   Fig.  62,  p.  145 
intradermic,   Fig.     118,  p.   257; 

Fig.  119,  p.  259 
Adrenal    body,    hyperplasia,    Fig. 

101,  p.  223 

hypoplasia,  Fig.  102,  p.  225 
normal,  Fig.  99,  p.  219;    Fig. 

IOO,  p.  221 

Amyloid  infiltration  of  kidney,  Fig. 

64,  p.  149 

of  liver,  Fig.  27,  p.  75 
of  spleen,  Fig.  38,  p.  97 

Angioma,  cavernous,  of  liver,  Fig. 

3i.  P-  83 

Appendix  vermiformis,  acute  in- 
flammation with  perforation 
Fig.  20,  p.  61 

chronic  obliterative  inflamma- 
tion, Fig.  21,  p.  63 
normal,  Fig.  19,  p.  59 
Artery,  atheroma,  Fig.  49,  p.  119 
calcification  of  middle  coat,  Fig. 

50,  p.  121 
endarteritis  obliterans,  Fig.  47, 

p.  115;   Fig.  48,  p.  117 
Atheroma,  artery,  Fig.  49,  p.  119 


B 


BLOOD,  acute  lymphatic  leukemia, 

Fig.  55,  p.  131 
leukocytosis,  Fig.  53,  p.  127 


j  Blood,  myelogenic  leukemia,  Fig. 

54,  p.  129 

normal,  Fig.  52,  p.  125 
Brain,    hemiplegia,    degeneration, 
annular         protuberance 
(pons),  Fig.  84,  p.  189 
cerebral  peduncles,  Fig.  83, 

p.  187 

medulla,  Fig.  85,  p.  191 
purulent     cerebral     meningitis, 

Fig.  93,  p.  207 

Breast,  fibroadenoma,  Fig.  80,  p. 
181 


CALCIFICATION,    middle    coat    of 

artery,  Fig.  50,  p.  121 
I  Capillary  bloodvessels,  Fig.  122,  p. 

265 
Carcinoma  basocellulare,  Fig.  114, 

p.  249 
of  breast,  Fig.  80,  p.  181;    Fig. 

81,  p.  185 
cylindrical  cell,  of  body  of  uterus, 

Fig.  76,  p.  173 
gland-cell,  of  pancreas,  Fig.  36, 

P-  93 

of  prostate,  Fig.  70,  p.  161 
of  pylorus,  Fig.  16,  p.  53 
secondary,  of  liver,  Fig.  33,  p.  87 

in  lymph  node,  Fig.  41,  p.  103 
spinocellulare,  of  skin,  Fig.  112, 

P-  245 

of  tongue,  Fig.  13,  p.  47 
squamous-cell,  of  neck  of  uterus, 

Fig.  77,  p.  175 
of  testicle,  Fig.  68,  p.  156 


270 


INDEX  TO  THE  ILLUSTRATIONS 


Cecum,  cylindrical-cell  carcinoma, 

Fig.  22,  p.  65 
Chancre  of  syphilis,  Fig.    123,  p. 

267;   Fig.  124,  p.  268 
Chorion-epithelioma,  Fig.   116,  p. 

253 

Cirrhosis  of  liver,  Laennec's  annu- 
lar, atrophic  form,  Fig.  28,  p.  77 
Congestion,    chronic    passive,    of 
liver,  Fig.  23,  p.  67;    Fig. 
24,  p.  69 

of  spleen,  Fig.  37^  p.  95 
of  liver    with  fatty  infiltration, 

Fig.  25,  p.  71 
Connective  tissue,  various  stages  of 

development,  Fig.  106,  p.  233 
Corpora  lutea  in  ovary,  Fig.  72,  p. 

x?5 

Cylindrical-cell    carcinoma  of    ce- 
cum,  Fig.  22,  p.  65 


DECIDUOMA   malignum,   Fig.    116, 
P-  253 


ECHINOCOCCUS  cyst  in  liver,  Fig. 

34.  P-  89 
Embolism,  septic,  of  kidney,  Fig. 

61,  p.  143;  Fig.  62,  p.  145 
Embryoma,  sacrococcygeal  tumor, 

Fig.  117,  p.  255 
Endocarditis,       ulcero-vegetative, 

Fig.  45,  p.  in 

Epithelial  pearl,  Fig.  113,  p.  247 
Epulis,  Fig.  1 1 1,  p.  243 


FALLOPIAN  tube,  inflammation  of 

(acute  salpingitis),  Fig.  79,  p.  179 

Fatty  degeneration  of  liver,   Fig. 

26,  p.  73 
of  muscle  of  heart,  Fig.  46,  p. 

U3 

infiltration  of  liver,  with  conges- 
tion, Fig.  25,  p.  71 


Fibroadenoma  of  mammary  gland, 

Fig.  80,  p.  181 

Fibroid  of  uterus,  Fig.  75,  p.  171 
Fibromyoma  of  uterus,  Fig.  75,  p. 

171 


GOITER,  colloid,  Fig.  97,  p.  215 
parenchymatous,  Fig.  98,  p.  217 


Heart,  acute  fibrinous  pericarditis, 

Fig.  44,  p.  109 
chronic  myocarditis,  Fig.  42,  p. 

105 
endocarditis,      ulcero-vegetative 

form,  Fig.  45,  p.  in 
fatty  infiltration  (cor  adiposum), 

Fig.  43,  p.  107 
metamorphosis  of  muscle,  Fig. 

46,  p.  113 
Hypernephroma  of  kidney,  Fig.  65, 

P-  151 

Hypophysis  cerebri,  normal,  Fig. 
103,  p.  227 


I 


ILEUM,  tuberculous  ulcer,  Fig.  18, 

P-  57 

typhoid  ulcer,  Fig.  17,  p.  55 
Infarction,    hemorrhagic   of   lung, 
Fig.  5,  p.  31 


KIDNEY,  amyloid  infiltration,  Fig. 

64,  p.  149 

chronic  nephritis,  Fig.  60,  p.  141 
hypernephroma  or  adenoma  of, 

Fig.  65,  p.  151 
normal,  Fig.  56,  p.  133;   Fig.  57, 

P-  135 

pyemic  nephritis,  with  abscesses, 
Fig.  61,  p.  143;  Fig.  62,  p.  145 

subacute  nephritis  (variolous  ne- 
phritis), Fig.  58,  p.  137;  Fig. 
59»  P-  139 


INDEX  TO  THE  ILLUSTRATIONS 


271 


Kidney,  tuberculous  pyelonephri- 
tic,  Fig.  63,  p.  147 


LEIOMYOMA,  Fig.  75,  p.  171 
Liver,  amyloid  infiltration  of,  Fig. 

.27..P-  75 
bile  pigmentation  of,  from  biliary 

obstruction,  Fig.  29,  p.  79 
biliary    abscess,    with    cirrhosis, 

Fig.  32,  p.  85 
cavernous  angioma  of,  Fig.  31. 

P-  83 
chronic  passive  congestion  of,  in 

heart  disease,  Fig.  23,  p.  67; 

Fig.  24,  p.  69 
congestion  and  fatty  infiltration, 

Fig.  25,  p.  71 
echinococcus  cyst  of,  Fig.  34,  p. 

89 

fatty  degeneration,  Fig.  26,  p.  73 
Laennec's  annular  atrophic  cir- 
rhosis of,  Fig.  28,  p.  77 
malaria   of,    with    hemozoin    or 

melanin  pigmentation,  Fig.  30, 

p.  81 
secondary  carcinoma  of,  Fig.  33, 

p.  87 
Lung,  bronchopneumonia,  Fig.  7, 

P-  35 
emphysema  and  congestion,  Fig. 

3.  P-  27 

stained  with  acid  orcein  to 

show  elastica,  Fig.  4,  p.  29 

fibrinous  or  croupous  pneumonia, 

Fig.  6,  p.  33 
hemorrhagic  infarction  of,  Fig.  5, 

P- 31 

massive     caseous      tuberculous 

pneumonia  of,  Fig.  1 1 ,  p.  43 
miliary  tuberculosis  of,  Fig.  8,  p. 

37;    Fig.  9,  p.  39 
normal,  Fig.  I,  p.  23 

stained    with    acid   orcein    to 

show  elastica,  Fig.  2,  p.  25 

tuberculous    bronchopneumonia 

of,  Fig.  10,  p.  41 

Lymph  node,  secondary  carcinoma 
of,  Fig.  41,  p.  103 


Lymph  node,  tuberculosis  of,  Fig. 

40,  p.  101 
Lymphocytoma,  Fig.  109,  p.  239 


MAMMA,  carcinoma  of,  Fig.  80,  p. 
181;   Fig.  81,  p.  185 

fibroadenoma  of,  Fig.  80,  p.  181 
Melanin,  Fig.  115,  p.  251 
Mixed  tumor,  sacrococcygeal  (em- 

bryoma),  Fig.  117,  p.  255 


NEVUS,  Fig.  115,  p.  251 


OSTEOSARCOMA,  Fig.    I IO,  p.  24! 

Ovary,  corpora  lutea  in,  Fig.  72, 

p.  165 
cystic  and  sclerotic,  Fig.  73,  p. 

167 
normal,  Fig.  71,  p.  163 


PANCREAS,  carcinoma  of,  Fig.  36, 

P-  93 
sclerosis  or  chronic  inflammation 

of,  Fig.  35,  p.  91 

Pericardium,    acute    fibrinous   in- 
flammation of,  Fig.  44,  p.  109 
Pigmentation,  biliary,  of  liver,  Fig. 

29,  p.  79 
hemozoin  or  melanin,   in  liver, 

Fig.  30,  p.  8 1 
Pituitary  body,  normal,  Fig.  103, 

p.  227;    Fig.  104,  p.  229 
Pleura,  tuberculosis  of,  with  sero- 
fibrinous  exudate,  Fig.  12,  p.  45 
Prostate,  carcinoma  of,  Fig.  70,  p. 

161 

hypertrophy  of,  Fig.  69,  p.  159 
Psammoma  of  the  meninges,  Fig. 
95.  P- 211 


272 


INDEX  TO  THE  ILLUSTRATIONS 


SALPINGITIS,  acute  gonococcic  form 

of,  Fig.  79,  p.  179 
Sarcoma,   giant-cell    (epulis),    Fig. 

in,  p.  243 

osteo-,  Fig.  no,  p.  241 
round-cell,  Fig.  108,  p.  237 
spindle-cell  (fibrosarcoma) ,  Fig. 

107,  p.  235 
Skin,  abscess  of,  Fig.  118,  p.  257; 

119,  p.  259 
sporotrichosis,  Fig.  120,  p.  261; 

Fig.  121,  p.  263 

Spinal  cord,  acute  anterior  polio- 
myelitis, Fig.  92,  p.  205 
disseminated  sclerosis,  Fig.  90, 

p.  201 

epidemic    cerebrospinal    men- 
ingitis of,  Fig.  94,  p.  209 
hemiplegia,     degeneration     of 
pyramidal  tracts,  cervical 
region,  Fig.  86,  p.  -193 
dorsal  region,  Fig.  87,  p.  195 
lumbar  region,  Fig.  88,  p.  197 
syringomyelia,  Fig.  91,  p.  203 
tabes  dorsalis,  Fig.  89,  p.  199 
Spleen,  amyloid  infiltration  of,  Fig. 

38,  p.  97 
chronic    passive    congestion    of, 

Fig.  37,  p.  95 
miliary  tuberculosis  of,  Fig.  39, 

p.  99 
Sporotrichosis  of  skin,  Fig.  120,  p. 

261;  Fig.  121,  p.  263 
Squamous-cell  carcinomaof  tongue, 

Fig.  13,  p.  47 
Stomach,    carcinoma    of    pylorus, 

Fig.  16,  p.  53 
simple  ulcer  of  pylorus,  Fig.  15, 

P-  5i 
Syncytioma  malignum,  Fig.  116,  p. 

Syphilis,  chancre,  or  primary  sore, 
Fig.  123,  p.  267;  Fig.  124,  p.  268 


TESTICLE,  carcinoma  of,  Fig.  68,  p. 

157 

normal,  of  dog,  Fig.  66,  p.  153 
tuberculosis  of,  Fig.  67,  p.  155 


Thrombosis   following    pulmonary 

embolism,  Fig.  5,  p.  31 
Thrombus  in  vein  of  obliterative 

phlebitis,  Fig.  51,  p.  123 
Thymus,  sclerotic,  Fig.  105,  p.  231 
Thyroid  gland  goiter,  colloid,  Fig. 

97,  P-  215 
parenchymatous,  Fig.  98,  p. 

217 

normal,  Fig.  96,  p.  213 
Tongue,  carcinoma  of,  spinocellu- 

lare,  Fig.  13,  p.  47 
tuberculosis  of,  Fig.  14,  p.  49 
Tuberculosis,    bronchopneumonia 


Fig.  10,  p.  41 
of  kidney,  Fig.  63,  p.  147 
of  lymph  node.  Fig.  40,  p. 


massive  caseous  pneumonia,  Fig. 

ii.  P- 43 

miliary,  of  lung,  Fig.  8,  p.  37; 

Fig-  9,  P-  39 
of  spleen,  Fig.  39,  p.  99 
of  pleura,  Fig.  12,  p.  45 
of  tongue,  Fig.  14,  p.  49 
ulcer  of  small  intestine,  Fig.  18, 

P- 57 

Typhoid  fever  ulcer  of  intestine, 
Fig.  17,  P.  55 

U 

ULCER,   simple,  of  stomach,   Fig. 

15,  P- 5i 

tuberculous,   of  small  intestine, 

Fig.  18,  p.  57 
typhoid,  of  intestine,  Fig.  17,  p. 

55 

Uterus,  carcinoma  of  body  of 
(adenocarcinoma;  cylindri- 
cal-cell carcinoma),  Fig.  76, 

P-  173 
squamous-cell,  of  neck  of,  Fig. 

77,  P-  175 
fibromyoma  (fibroid),  Fig.  75,  p. 

171 

normal,  Fig.  74,  p.  169 
ulcerative  cervical  metritis,  Fig. 

78,  p.  177 

VEIN,   obliterative   phlebitis,    Fig. 
51,  P-  123 


INDEX  TO  THE  TEXT. 


ABB£  condenser,  17 
Abscess,  biliary,  of  liver,  84 

intradermic,  256 
Acid  orcein  stain,  21 
Acanthosis,  48 
Adenocarcinoma  of  liver,  86 

of  pancreas,  92 

Adrenal  body,  hyperplasia  ot,  222 
hypoplasia  of,  224 
normal  histology  of,  218 
Atelectasis,  24 
Alveolitis,  catarrhal,  36 

fibrinous,  24,  32,  34 

hemorrhagic,  24,  26 

pttrulent,  24,  32,  34,  36 

serous,  24,  34,  36 
Amyloid  disease  of  kidney,  148 

infiltration  of  spleen,  96 

liver,  74 

reaction,  74 

substance,  nature  of,  96 
Angioma,  cavernous,  of  liver,  82 
Anthracosis,  22 
Artery,  atheroma  of,  118 

calcification  of,  120 

endarteritis  obliterans  of ,  114 

normal  histology  of,  114 

pipe-stem,  120 
Atheroma  or  artery,  118 
Atrophy  of  liver  cells,  74,  76 


Bile  capillaries,  normal,  66 
Blood,  myelogenic  leukemia,  128 
leukocytosis,  126 
lymphatic  leukemia,  130 
normal  histology  of,  124 
red  corpuscles  of,  124 
basophils,  124 
eosinophils,  124 
lymphocytes,  124 
polymorphonuclears,   124 
white  corpuscles  of,  124 
Brain,  cerebrum,  hemiplegia  of,  186 
descending  degeneration  of  pyra- 
midal tract  of,  1 86 
purulent  leptomeningitis  of,  206 
Breast,  cancer  of,  182 

fibroadenoma  of,  180 
Bright's  disease,  140 
Bronchopneumonia,  34 
tuberculous,  40 


B 

BICHLORIDE    of    mercury, 
deposit  from,  98 
18 


CALCIFICATION  of  arterial  wall,  120 

of  artery,  120 

psammoma  of  meninges,  210 
Cancer  of  breast,  182 

of  cervix  uteri,  174 

embolus,  86 

of  pancreas,  92 

of  prostate,  160 

secondary,  of  liver,  86 
in  lymph  node,  100 

of  testicle,  156 

of  uterine  body,  172 
black    Capillary  vessels,  264 

Carcinoma,  basocellulare,  248 


274 


INDEX  TO   THE  TEXT 


Carcinoma  of  cecum,  64 
of  pylorus,  52 
spinocellulare,  46,  174,  244 
squamous    cell    of    cervix  uteri, 

174 

Caseation,  40,  42 
Cecum,  cancer  of,  64 
Cerebrospinal  meningitis,  208 
Chancre,  syphilitic,  266 
Cholesterin       in       atheromatous 

artery,  118 
Chondrin,  240 
Chorion,  epithelioma,  252 
Chromaffine  cells,  220 
Chromatolysis,  256 
Chromatophores,  250 
Chromophobic  cells,  226 
Cirrhosis  of  liver,  76 
Collagen,  232 

Congestion,     chronic    passive,     of 
spleen,  94 

passive,  of  the  liver,  66,  70 

pulmonary,  26 
Connective  tissue,  232 
Coradiposum,  106 
Corpus  luteum  in  the  ovary,  164 
Corpuscles  of  Hassal  in  thymus, 

230 

Corrosive  sublimate,  20 
Crenation    of    blood    corpuscles, 

128 
Crystals  of  fatty  acids  in  atheroma, 

118 

Cutting  sections,  20 
Cylindrical-cell    carcinoma   of   ce- 
cum, 64 

epithelioma  of  body  of  uterus, 

172 

of  liver,  86 
Cyst,  echinococcus,  of  liver,  88 

hydatid,  of  liver,  88 


DECIDUOMA,  252 
Desquamation  of  epithelium,  32 
Disseminated  sclerosis,  spinal  cord, 

200 

Dyskeratosis,  246 


E 


ECHINOCOCCUS  cyst  of  liver,  88 
Embolism,  microorganismal  in  kid- 
ney, 142 

pulmonary,  30 
Embolus,  cancer,  86 
Emphysema,  24 

essential,  28 

pulmonary,  26 
Endarteritis  obliterans,  114 

ulcero-vegetative,  no 
Eosin,  21 
Eosinophilia,  88 
Epididymis,   normal  histology  of, 

152 
Epithelial  pearls,  46 

in  carcinoma  spinocellulare,244 
Epulis,  242 


F 


FALLOPIAN  tube,  acute  inflamma- 
tion of,  178 

False  membranes,  32,  44 

in  acute  pericarditis,  108 

Fatty  acid  crystals  in  atheroma, 

118 

degeneration  of  liver,  73 
infiltration  of  liver,  71 

Fibin,  32,  44 

Fibroadenoma  of  breast,  180 

Fibroblasts,  232 

Fibromyoma  of  uterus,  170 

Fibrosis  of  cardiac  muscle,  104 

Fixation,  19 

Follicles  of  Naboth,  176 

Formaldehyde,  20 


GENTIAN  violet  for  amyloid  test, 

74.  96 
Giant  cells,  foreign  body,  38 

in  sporotrichosis,  260 

of  tuberculosis,  38 

of  tumors,  38 

Gliosis  in  syringomyelia,  202 
Goiter,  colloid,  214 


INDEX  TO  THE  TEXT 


275 


HASSAL,  corpuscles  of,  in  thymus, 
230 

Heart,  acute  fibrinous  pericarditis 
of,  1 08 

chronic  myocarditis  of,  104 
endocarditis    of,    ulcero-vegeta- 

tive,  no 

fatty  degeneration  of,  112 
myocardial  fragmentation  of ,  105 
normal  histology  of,  104 
obese,  106 

in  pernicious  anemia,  112 
tabby  mottling,  112 

Hematoidin,  30 

Hematoxylon,  21 

Hemiplegia,  186 

Hemozoin,  80 

Hepatization,  red,  32 
gray,  32 

Hyaline  bodies  in  psammoma,  210  \ 
degeneration  of  vessel,  114 

Hydatid  cyst  of  liver,  88 

Hydromyelia,  spinal  cord,  202 

Hypernephroma  of  kidney,  150 

Hypertrophy  of  prostate,  1 58 

Hypophysis  cerebri,  normal  histol- 
ogy of,  226 


I 


IMBEDDING,  20 

Infarction,  hemorrhagic,  30 

Infiltration,  amyloid,  of  liver,  74 

fatty,  of  liver,  70 
Inflammation,  abscess  of  liver,  84 
of  skin,  256,  260 

of  alveoli  of  lung,  24,  32,  34,  36 

endocarditis,  no 

of  Fallopian  tube,  178 

of  kidney,  142,  144 

of  neck  of  uterus,  176 

of  pericardium,  108 

proud  flesh,  236 

round-cell  infiltration,  46 

serofibrinous,  44 

thrombosing,  of  vein,  122 

ulcer  of  stomach,  50 
Intestine,  typhoid  ulcer  of  ileum,  54 
Iris  diaphragm,  18 


KERATINIZATION  of  epithelial  cells, 

244 
of  epithelium,  46 

Kidney,  adenoma  of,  150 
amyloid  infiltration  of,  148 
hypernephroma,  benign,  150 
glomerules,  132 
Malpighian  bodies  of,  132 
normal  histology  of,  132 
pyramids  of  Ferrein,  148 
subacute  nephritis  of,  136 
tuberculous  pyelonephritis,  146 

Kupffer's  cells,  80 


LAENNEC'S  cirrhosis  of  liver,  76 
Langerhans,  islands  of,  in  pancreas, 

90 

Langhans,  cells  of,  253 
Large  intestine,  normal  histology 

of,  64 

Leiomyoma  of  uterus,  170 
Leptomeningitis,  purulent,  206 
Leukemia,  lymphatic,  130 

myelogenic,  128 
Leukocytes,  acidophilic,  88 

eosinophilic,  88 
Leukocytosis,  124 
Leukoplakia,  46,  244 
Liver,  amyloid  infiltration,  74 

annular  cirrhosis  of,  77 

atrophic  cirrhosis  of,  76 

biliary  abscess  of,  84 
pigmentation  of,  78 

bivenous  cirrhosis  of,  76 

cavernous  angioma  of,  82 

of  chronic  cardiac  disease,  66 
passive  congestion  of,  66 

cirrhosis,  76,  84 

echinococcus  cyst  of,  88 

fatty  and  congested,  70 
degeneration  of,  72 
infiltration  of,  70 
metamorphosis  of,  72 

hob-nail,  77 

hydatid  cyst  of,  88 

inverted  lobule,  68 


276 


INDEX  TO  THE  TEXT 


Liver,  malarial  pigmentation,  80 

monocellular  dislocation,  68,  70 

normal  histology  of,  66 

nutmeg,  68 

pseudocanaliculi,  76,  84 

secondary  cancer  of,  86 
Lugol's  solution  for  amyloid  test, 

74.96 
Lung,  bronchopneumonia  of,  34 

carbon  particles  in,  22 

congestion  of,  26 

elastic  tissue  in,  22 

embolism  of,  30 

emphysema  of,  26 

fibrinous  pneumonia  of,  32 

infarction  of ,  30 

massive  caseous  pneumonia  of  ,42 

miliary  tuberculosis  of,  36 

normal  histology  of,  22 

serofibrinous  pleuritis,  44 

tuberculous  bronchopneumonia, 

40 
Lymph  node,  normal  histology  of, 

100 

secondary  cancer  of,  100 
tuberculosis  of,  100 
Lymphadenoma,  236,  238 
Lymphocytoma,  238 


M 


MACROPHAGES,  30,  118,  256 
Malaria,  pigmentation  of  liver,  80 
Malignant  tumor,  method  of  inva- 
sion, 52 

metastasis  of,  52 

Malpighian  corpuscle  of  spleen,  94 
Mamma,  cancer  of,  182 

fibroadenoma  of,  180 
Margination  of  leukocytes,  264 
Medulla  oblongata,  190 
Melanin,  80,  250 
Metaplasia,  240 
Metritis,  ulceration  of  cervix  uteri, 

176 

Microphages,  256 
Microscope,  methods  of  using,  17 
Mirror,  18 
Mixed    tumor    of    sacrococcygeal 

region,  254 


Muscle,  cardiac,  104 
Myelocytes  in  leukemia,  128 
Myeloplaxes,  242 
Myocarditis,  chronic,  104 


N 


NABOTHIAN  follicles,  176 
Nevus  pjgmentosus,  250 

of  skin,  250 
Nephritis,  ascending  radiating,  144 

chronic,  140 

desquamative  tubulitis,  138 

embolic,  142 

exudative  tubulitis,  138 

mixed,  138 

pyelo-,  144 

pyemic,  142 

subacute,  136 

tuberculous  pyelo-,  146 
Neuronophagia  in  poliomyelitis, 204 
Normoblasts,  128 
Nutmeg  liver,  68 


O 


OBJECTIVES,  18 

Orcein,  elastic  stain  in  endarteritis 

obliterans,  116 

Organization  of  a  thrombus,  30 
Osmic  acid  stain  for  fat,  112 
Ossein,  240 
Osteoblasts,  240 
Osteosarcoma,  240 
Ovary,  corpus  luteum  of,  164 

normal  histology  of,  162 

sclerocyclic,  166 
Oxyuris,  60 


PANCREAS,  adenocarcinoma  of,  92 

islands  of  Langerhans  in,  90 

normal  histology  of,  90 

sclerosis  of,  90 
Periangiocholitis,  84 
Pericarditis,  acute  fibrinous,  108 
Phagocytes,       mononuclear,       in 

spleen,  94 


INDEX  TO  THE  TEXT 


277 


Phlebitis,  obliterative,  122 

throm  bosing,  122 
Phlegmasia  alba  dolens,  122 
Pigmentation,  biliary,  of  liver,  78 

malarial,  of  liver,  80 
Pituitary  body,  normal  histology 

of,  226 

Plasmocytes,  256,  266 
Plasmoma,  266 
Pleuritis,  serofibrinous,  44 
Pneumonia,  fibrinous,  32 

massive  caseous,  42 
Poikilocytes,  128 

Poliomyelitis,  anterior  acute,  204 
Prepuce,  chancre  of,  266 
Prostate,  158 

adenoma  of,  158 

cancer  of,  160 

hypertrophy  of,  158 
Proud  flesh,  236 
Psammoma,  210 
Pycnosis,  34 
Pyophages,  256 


RODENT  ulcer,  248 


SACROCOCCYGEAL  tumor,  254 
Salpingitis,  acute,  178 
Sarcoma,  fibro-,  234 

giant-cell,  242 

globo-cellulare,  236 

osteogenetic,  240 

osteosarcoma  of  gum,  242 

round-cell,  236 

spindle-cell,  234 
Sclerosis  of  pancreas,  90 
Seal-ring  appearance  of  liver  cells, 

Section-cutting,  20 

Sections,  methods  of  interpreting, 

17 

Seminoma,  156 
Skin,  abscess  of,  256 

chancre  of,  266 

nevus  of,  250 


Skin,  sporotrichosis  of,  260 
squamous-cell  carcinoma  of,  244, 

248 

Spinal  cord,  acute  anterior  polio- 
myelitis of,  204 
cervical,  192 

disseminated  sclerosis  of,  200 
dorsal,  194 

epidemic  cerebrospinal  menin- 
gitis of,  208 
lumbar,  196 
syringomyelia  of,  202 
tabes  dorsalis  of,  198 
Spleen,  amyloid  infiltration  of,  96 
chronic  passive  congestion  of,  94 
Malpighian  corpuscle  of,  94 
normal  histology  of,  94 
pulp  of,  red,  94 

white,  94 
tuberculosis  of ,  98 
Spongiocytes,  218 
Sporotrichosis,  260 
Squamous-cell  carcinoma  of  cervix 

uteri,  174 
of  skin,  244 
of  tongue,  46 
Staining,  21 

Stains  for  nervous  tissue  study,  186 
Stomach,  cancer  of  pylorus,  52 
normal  histology  of,  50 
ulcer  of  pyloris,  50 
Small  intestine,  normal  histology 

of,  54 

tuberculous  ulcer  of,  56 
Suprarenal  gland,  normal  histology 

of,  218 

Sympexions  in  prostate  gland,  158 
Syncytioma  malignum,  252 
Syphilis,  chancre,  266 
Syringomyelia  of  spinal  cord,  202 


TABES  dorsalis  of  spinal  cord,  198 
Testicle,  cancer  of,  156 

normal  histology  of,  1 52 

tuberculosis  of,  152 
Thrombus,  organization  of,  30 

venous,  122 
Thyroid  gland,  colloid  goiter  of,  214 


278 


INDEX  TO  THE  TEXT 


Thyroid  gland,  fetal  goiter  of,  216 
normal  histology  of,  212 
parenchymatous  goiter  of,  216 
sclerosis  of,  230 
Tongue,    carcinoma   spinocellulare 

of,  46 

tuberculosis  of,  48 
Transmigration  of  leukocytes,  264 
Tube  casts  in  tubules  of  kidney,  140 
Tuberculosis  of  kidney,  146 

of  lung,  serofibrinous  pleuritis,  44 
of  lymphatic  node,  100 
miliary,  histology  of,  36,38 

of  lung,  36 
of  spleen,  98 
of  testicle,  152 
of  tongue,  48 
ulceration  of  intestine,  56 
Tubular  epithelioma,  248 
Tumor,  angioma,  82 

carcinoma,  adenocarcinoma,  86, 

92 

cylindrical-cell,  64,  86,  160,  172 
gland-cell,  52,  92,  156,  182 
secondary,  86,  100 
spinocellulare,  46,  174,  244 
squamous-cell,carcinoma  baso- 

cellulare,  248 
chorion  epithelioma,  252 
deciduoma  malignum,  252 
hypernephroma,  150 
lymphadenoma,  236,238 
mixed,  254 
nevus,  250 
psammoma,  210 
sarcoma,  fibro-,  234 


Tumor,  sarcoma,  giant-cell,  242- 

osteosarcoma,  240 

round-cell.  236 

spindle-cell,  234 
syncytioma  malignum,  252 
Typhoid  fever,  intestinal  ulcer,  54. 


ULCER  of  cervix  uteri,  176 
of  pyloris,  50 

tuberculous,  of  intestine,  56 
Uterus,  cancer  of  body,  172 

of  cervix,  174 
fibromyoma  of,  170 
inflammation  of  muscle  of  neck 

of,  176 
normal  histology  of,  168 


VAN  GIESEN'S  stain,  21 

Vein,  obliterative  phlebitis,  122 

Vermiform  appendix,  chronic  oblit- 
erative appendicitis,  62 
normal  histology  ot,  58 
perforative  appendicitis,  60 

Vomica,  38 


W 


WALLERIAN    degeneration    of    the 
central  nervous  system,  186 


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